]> 2015-3-25 Arbor version; 1.2.92 en Jiangan Xie (Hardy) IDOBRU: Brucellosis Ontology Salwa Ali (S.A.) (contributed the epidemiology related terms) http://www.infectiousdiseaseontology.org/Home.html en Edison Ong Asiyah Yu Lin (YL) Brucellosis Ontology is a biomedical ontology in the domain of zoonotic disease brucellosis that is caused by Brucella, a facultative intracellular baterium. OWL-DL The Brucellosis Ontology (IDOBRU) as an extension of the Infectious Disease Ontology (IDO) Yongqun "Oliver" He (YH) Zuoshuang "Allen" Xiang release version BFO OWL specification label Really of interest to developers only Relates an entity in the ontology to the name of the variable that is used to represent it in the code that generates the BFO OWL file from the lispy specification. BFO CLIF specification label Person:Alan Ruttenberg Really of interest to developers only Relates an entity in the ontology to the term that is used to represent it in the the CLIF specification of BFO2 editor preferred term editor preferred label editor preferred term GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Daniel Schober The concise, meaningful, and human-friendly name for a class or property preferred by the ontology developers. (US-English) editor preferred label editor preferred term example of usage A phrase describing how a class name should be used. May also include other kinds of examples that facilitate immediate understanding of a class semantics, such as widely known prototypical subclasses or instances of the class. Although essential for high level terms, examples for low level terms (e.g., Affymetrix HU133 array) are not GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Daniel Schober example in branch An annotation property indicating which module the terms belong to. This is currently experimental and not implemented yet. GROUP:OBI OBI_0000277 in branch has curation status OBI_0000281 PERSON:Alan Ruttenberg PERSON:Bill Bug PERSON:Melanie Courtot has curation status definition textual definition definition definition definition GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Daniel Schober The official OBI definition, explaining the meaning of a class or property. Shall be Aristotelian, formalized and normalized. Can be augmented with colloquial definitions. The official definition, explaining the meaning of a class or property. Shall be Aristotelian, formalized and normalized. Can be augmented with colloquial definitions. definition editor note editor note An administrative note intended for its editor. It may not be included in the publication version of the ontology, so it should contain nothing necessary for end users to understand the ontology. GROUP:OBI:<http://purl.obfoundry.org/obo/obi> PERSON:Daniel Schober editor note definition editor definition editor term editor 20110707, MC: label update to term editor and definition modified accordingly. See http://code.google.com/p/information-artifact-ontology/issues/detail?id=115. GROUP:OBI:<http://purl.obolibrary.org/obo/obi> Name of editor entering the definition in the file. The definition editor is a point of contact for information regarding the term. The definition editor may be, but is not always, the author of the definition, which may have been worked upon by several people Name of editor entering the term in the file. The term editor is a point of contact for information regarding the term. The term editor may be, but is not always, the author of the definition, which may have been worked upon by several people PERSON:Daniel Schober definition editor term editor alternative term alternative term An alternative name for a class or property which means the same thing as the preferred name (semantically equivalent) GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Daniel Schober alternative term definition source definition source Discussion on obo-discuss mailing-list, see http://bit.ly/hgm99w GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Daniel Schober definition source formal citation, e.g. identifier in external database to indicate / attribute source(s) for the definition. Free text indicate / attribute source(s) for the definition. EXAMPLE: Author Name, URI, MeSH Term C04, PUBMED ID, Wiki uri on 31.01.2007 has obsolescence reason PERSON:Alan Ruttenberg PERSON:Melanie Courtot Relates an annotation property to an obsolescence reason. The values of obsolescence reasons come from a list of predefined terms, instances of the class obsolescence reason specification. has obsolescence reason curator note curator note An administrative note of use for a curator but of no use for a user PERSON:Alan Ruttenberg curator note is denotator type Alan Ruttenberg In OWL 2 add AnnotationPropertyRange('is denotator type' 'denotator type') relates an class defined in an ontology, to the type of it's denotator is denotator type imported from imported from For external terms/classes, the ontology from which the term was imported GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Alan Ruttenberg PERSON:Melanie Courtot imported from expand expression to Chris Mungall A macro expansion tag applied to an object property (or possibly a data property) which can be used by a macro-expansion engine to generate more complex expressions from simpler ones ObjectProperty: RO_0002104 Label: has plasma membrane part Annotations: IAO_0000424 "http://purl.obolibrary.org/obo/BFO_0000051 some (http://purl.obolibrary.org/obo/GO_0005886 and http://purl.obolibrary.org/obo/BFO_0000051 some ?Y)" expand expression to expand assertion to A macro expansion tag applied to an annotation property which can be expanded into a more detailed axiom. Chris Mungall ObjectProperty: RO??? Label: spatially disjoint from Annotations: expand_assertion_to "DisjointClasses: (http://purl.obolibrary.org/obo/BFO_0000051 some ?X) (http://purl.obolibrary.org/obo/BFO_0000051 some ?Y)" expand assertion to first order logic expression PERSON:Alan Ruttenberg first order logic expression antisymmetric property Alan Ruttenberg antisymmetric property part_of antisymmetric property xsd:true use boolean value xsd:true to indicate that the property is an antisymmetric property OBO foundry unique label The intended usage of that property is as follow: OBO foundry unique labels are automatically generated based on regular expressions provided by each ontology, so that SO could specify unique label = 'sequence ' + [label], etc. , MA could specify 'mouse + [label]' etc. Upon importing terms, ontology developers can choose to use the 'OBO foundry unique label' for an imported term or not. The same applies to tools . An alternative name for a class or property which is unique across the OBO Foundry. GROUP:OBO Foundry <http://obofoundry.org/> OBO foundry unique label PERSON:Alan Ruttenberg PERSON:Bjoern Peters PERSON:Chris Mungall PERSON:Melanie Courtot elucidation has associated axiom(nl) has associated axiom(fol) has axiom label term replaced by Person:Alan Ruttenberg Person:Alan Ruttenberg Use on obsolete terms, relating the term to another term that can be used as a substitute term replaced by NCBI GeneID Oliver He, Yue Liu A GeneID in the NCBI Gene database NCBI LocusTag Oliver He, Yue Liu the NCBI LocusTag name of a gene modification date a date of content modification Oliver He, Yue Liu organism NCBITaxon ID The NCBITaxon ontology ID of an organism. Oliver He, Yue Liu chromosome ID of gene A chromosome ID where a gene is located. Oliver He type of gene Oliver He an annotation property that specifies the type of a gene nomenclature status an annotation property that specifies a nomenclature status Oliver He has PubMed association Yongqun He An annotation property that represents a gene's association with PubMed publication(s). temporal interpretation https://code.google.com/p/obo-relations/wiki/ROAndTime An assertion that holds between an OWL Object Property and a temporal interpretation that elucidates how OWL Class Axioms that use this property are to be interpreted in a temporal context. logical macro assertion https://code.google.com/p/obo-relations/wiki/ShortcutRelations An assertion that holds between two classes that is intended to be expanded into one or more logical axioms. The logical expansion can yield axioms expressed using any formal logical system, including, but not limited to OWL2-DL. logical macro assertion on a property A logical macro assertion whose domain is an IRI for a property logical macro assertion on an object property has_rank A metadata relation between a class and its taxonomic rank (eg species, family) ncbi_taxonomy Contributor An entity responsible for making contributions to the content of the resource. Examples of a Contributor include a person, an organisation, or a service. Typically, the name of a Contributor should be used to indicate the entity. Coverage Coverage will typically include spatial location (a place name or geographic coordinates), temporal period (a period label, date, or date range) or jurisdiction (such as a named administrative entity). Recommended best practice is to select a value from a controlled vocabulary (for example, the Thesaurus of Geographic Names [TGN]) and that, where appropriate, named places or time periods be used in preference to numeric identifiers such as sets of coordinates or date ranges. The extent or scope of the content of the resource. Creator An entity primarily responsible for making the content of the resource. Examples of a Creator include a person, an organisation, or a service. Typically, the name of a Creator should be used to indicate the entity. Date A date associated with an event in the life cycle of the resource. Typically, Date will be associated with the creation or availability of the resource. Recommended best practice for encoding the date value is defined in a profile of ISO 8601 [W3CDTF] and follows the YYYY-MM-DD format. Description An account of the content of the resource. Description may include but is not limited to: an abstract, table of contents, reference to a graphical representation of content or a free-text account of the content. Format The physical or digital manifestation of the resource. Typically, Format may include the media-type or dimensions of the resource. Format may be used to determine the software, hardware or other equipment needed to display or operate the resource. Examples of dimensions include size and duration. Recommended best practice is to select a value from a controlled vocabulary (for example, the list of Internet Media Types [MIME] defining computer media formats). Resource Identifier An unambiguous reference to the resource within a given context. Recommended best practice is to identify the resource by means of a string or number conforming to a formal identification system. Example formal identification systems include the Uniform Resource Identifier (URI) (including the Uniform Resource Locator (URL)), the Digital Object Identifier (DOI) and the International Standard Book Number (ISBN). Language A language of the intellectual content of the resource. Recommended best practice is to use RFC 3066 [RFC3066], which, in conjunction with ISO 639 [ISO639], defines two- and three-letter primary language tags with optional subtags. Examples include "en" or "eng" for English, "akk" for Akkadian, and "en-GB" for English used in the United Kingdom. Publisher An entity responsible for making the resource available Examples of a Publisher include a person, an organisation, or a service. Typically, the name of a Publisher should be used to indicate the entity. Relation Recommended best practice is to reference the resource by means of a string or number conforming to a formal identification system. A reference to a related resource. Rights Management Typically, a Rights element will contain a rights management statement for the resource, or reference a service providing such information. Rights information often encompasses Intellectual Property Rights (IPR), Copyright, and various Property Rights. If the Rights element is absent, no assumptions can be made about the status of these and other rights with respect to the resource. Information about rights held in and over the resource. Source A reference to a resource from which the present resource is derived. The present resource may be derived from the Source resource in whole or in part. Recommended best practice is to reference the resource by means of a string or number conforming to a formal identification system. Subject and Keywords The topic of the content of the resource. Typically, a Subject will be expressed as keywords, key phrases or classification codes that describe a topic of the resource. Recommended best practice is to select a value from a controlled vocabulary or formal classification scheme. Title Typically, a Title will be a name by which the resource is formally known. A name given to the resource. Resource Type The nature or genre of the content of the resource. Type includes terms describing general categories, functions, genres, or aggregation levels for content. Recommended best practice is to select a value from a controlled vocabulary (for example, the DCMI Type Vocabulary [DCMITYPE]). To describe the physical or digital manifestation of the resource, use the Format element. has_alternative_id has_broad_synonym database_cross_reference has_exact_synonym has_narrow_synonym has_obo_namespace has_related_synonym in_subset shorthand part_of part of part of Everything is part of itself. Any part of any part of a thing is itself part of that thing. Two distinct things cannot be part of each other. http://www.obofoundry.org/ro/#OBO_REL:part_of OBO Relation Ontology Occurrents are not subject to change and so parthood between occurrents holds for all the times that the part exists. Many continuants are subject to change, so parthood between continuants will only hold at certain times, but this is difficult to specify in OWL. See https://code.google.com/p/obo-relations/wiki/ROAndTime a core relation that holds between a part and its whole is part of my brain is part of my body (continuant parthood, two material entities) my stomach cavity is part of my stomach (continuant parthood, immaterial entity is part of material entity) part_of this day is part of this year (occurrent parthood) has_part has part has_part Everything has itself as a part. Any part of any part of a thing is itself part of that thing. Two distinct things cannot have each other as a part. Occurrents are not subject to change and so parthood between occurrents holds for all the times that the part exists. Many continuants are subject to change, so parthood between continuants will only hold at certain times, but this is difficult to specify in OWL. See https://code.google.com/p/obo-relations/wiki/ROAndTime a core relation that holds between a whole and its part has part has_part my body has part my brain (continuant parthood, two material entities) my stomach has part my stomach cavity (continuant parthood, material entity has part immaterial entity) this year has part this day (occurrent parthood) inheres in at all times inheresInAt BFO2 Reference: independent continuant that is not a spatial region inheres-in_at BFO2 Reference: specifically dependent continuant Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'inheres in at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'inheres in@en(x,y,t)'. (iff (inheresInAt a b t) (and (DependentContinuant a) (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))) // axiom label in BFO2 CLIF: [051-002] BFO 2 Reference: Inherence is a subrelation of s-depends_on which holds between a dependent continuant and an independent continuant that is not a spatial region. Since dependent continuants cannot migrate from one independent continuant bearer to another, it follows that if b s-depends_on independent continuant c at some time, then b s-depends_on c at all times at which a exists. Inherence is in this sense redundantly time-indexed.For example, consider the particular instance of openness inhering in my mouth at t as I prepare to take a bite out of a donut, followed by a closedness at t+1 when I bite the donut and start chewing. The openness instance is then shortlived, and to say that it s-depends_on my mouth at all times at which this openness exists, means: at all times during this short life. Every time you make a fist, you make a new (instance of the universal) fist. (Every time your hand has the fist-shaped quality, there is created a new instance of the universal fist-shaped quality.) b inheres_in c at t =Def. b is a dependent continuant & c is an independent continuant that is not a spatial region & b s-depends_on c at t. (axiom label in BFO2 Reference: [051-002]) b inheres_in c at t =Def. b is a dependent continuant & c is an independent continuant that is not a spatial region & b s-depends_on c at t. (axiom label in BFO2 Reference: [051-002]) (iff (inheresInAt a b t) (and (DependentContinuant a) (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))) // axiom label in BFO2 CLIF: [051-002] bearer of at some time Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'bearer of at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'bearer of@en'(x,y,t) BFO2 Reference: independent continuant that is not a spatial region bearerOfAt (iff (bearerOfAt a b t) (and (specificallyDependsOnAt b a t) (IndependentContinuant a) (not (SpatialRegion a)) (existsAt b t))) // axiom label in BFO2 CLIF: [053-004] b bearer_of c at t =Def. c s-depends_on b at t & b is an independent continuant that is not a spatial region. (axiom label in BFO2 Reference: [053-004]) bearer-of_st BFO2 Reference: specifically dependent continuant b bearer_of c at t =Def. c s-depends_on b at t & b is an independent continuant that is not a spatial region. (axiom label in BFO2 Reference: [053-004]) (iff (bearerOfAt a b t) (and (specificallyDependsOnAt b a t) (IndependentContinuant a) (not (SpatialRegion a)) (existsAt b t))) // axiom label in BFO2 CLIF: [053-004] realized in [copied from inverse property 'realizes'] to say that b realizes c at t is to assert that there is some material entity d & b is a process which has participant d at t & c is a disposition or role of which d is bearer_of at t& the type instantiated by b is correlated with the type instantiated by c. (axiom label in BFO2 Reference: [059-003]) Paraphrase of elucidation: a relation between a realizable entity and a process, where there is some material entity that is bearer of the realizable entity and participates in the process, and the realizable entity comes to be realized in the course of the process (forall (x y z t) (if (and (RealizableEntity x) (Process y) (realizesAt y x t) (bearerOfAt z x t)) (hasParticipantAt y z t))) // axiom label in BFO2 CLIF: [106-002] [copied from inverse property 'realizes'] to say that b realizes c at t is to assert that there is some material entity d & b is a process which has participant d at t & c is a disposition or role of which d is bearer_of at t& the type instantiated by b is correlated with the type instantiated by c. (axiom label in BFO2 Reference: [059-003]) realizedIn realized-in if a realizable entity b is realized in a process p, then p stands in the has_participant relation to the bearer of b. (axiom label in BFO2 Reference: [106-002]) is realized by realized in realized_in this disease is realized in this disease course this fragility is realized in this shattering this investigator role is realized in this investigation if a realizable entity b is realized in a process p, then p stands in the has_participant relation to the bearer of b. (axiom label in BFO2 Reference: [106-002]) (forall (x y z t) (if (and (RealizableEntity x) (Process y) (realizesAt y x t) (bearerOfAt z x t)) (hasParticipantAt y z t))) // axiom label in BFO2 CLIF: [106-002] realizes realizes Paraphrase of elucidation: a relation between a process and a realizable entity, where there is some material entity that is bearer of the realizable entity and participates in the process, and the realizable entity comes to be realized in the course of the process realizes (forall (x y t) (if (realizesAt x y t) (and (Process x) (or (Disposition y) (Role y)) (exists (z) (and (MaterialEntity z) (hasParticipantAt x z t) (bearerOfAt z y t)))))) // axiom label in BFO2 CLIF: [059-003] realizes this disease course realizes this disease this investigation realizes this investigator role this shattering realizes this fragility to say that b realizes c at t is to assert that there is some material entity d & b is a process which has participant d at t & c is a disposition or role of which d is bearer_of at t& the type instantiated by b is correlated with the type instantiated by c. (axiom label in BFO2 Reference: [059-003]) (forall (x y t) (if (realizesAt x y t) (and (Process x) (or (Disposition y) (Role y)) (exists (z) (and (MaterialEntity z) (hasParticipantAt x z t) (bearerOfAt z y t)))))) // axiom label in BFO2 CLIF: [059-003] to say that b realizes c at t is to assert that there is some material entity d & b is a process which has participant d at t & c is a disposition or role of which d is bearer_of at t& the type instantiated by b is correlated with the type instantiated by c. (axiom label in BFO2 Reference: [059-003]) participates in participates in at some time participates-in_st [copied from inverse property 'has participant at some time'] BFO2 Reference: independent continuant that is not a spatial region, specifically dependent continuant, generically dependent continuant [copied from inverse property 'has participant at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has participant at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has participant@en'(x,y,t) [copied from inverse property 'has participant at some time'] BFO2 Reference: process participatesInAt [copied from inverse property 'has participant at some time'] BFO 2 Reference: Spatial regions do not participate in processes. [copied from inverse property 'has participant at some time'] has_participant is an instance-level relation between a process, a continuant, and a temporal region at which the continuant participates in some way in the process. (axiom label in BFO2 Reference: [086-003]) participates in participates_in has participant at some time (forall (x y t) (if (and (hasParticipantAt x y t) (SpecificallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t) (specificallyDependsOnAt y z t))))) // axiom label in BFO2 CLIF: [090-003] hasParticipantAt (forall (x y t) (if (hasParticipantAt x y t) (existsAt y t))) // axiom label in BFO2 CLIF: [089-001] has-participant_st BFO2 Reference: process (forall (x y t) (if (and (hasParticipantAt x y t) (GenericallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (genericallyDependsOn y z t) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [091-003] (forall (x y t) (if (hasParticipantAt x y t) (Occurrent x))) // axiom label in BFO2 CLIF: [087-001] (forall (x y t) (if (hasParticipantAt x y t) (Continuant y))) // axiom label in BFO2 CLIF: [088-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has participant at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has participant@en'(x,y,t) BFO 2 Reference: Spatial regions do not participate in processes. BFO2 Reference: independent continuant that is not a spatial region, specifically dependent continuant, generically dependent continuant has_participant is an instance-level relation between a process, a continuant, and a temporal region at which the continuant participates in some way in the process. (axiom label in BFO2 Reference: [086-003]) if b has_participant c at t & c is a generically dependent continuant, then there is some independent continuant that is not a spatial region d, and which is such that c g-depends on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [091-003]) if b has_participant c at t & c is a specifically dependent continuant, then there is some independent continuant that is not a spatial region d, c s-depends_on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [090-003]) if b has_participant c at t then b is an occurrent. (axiom label in BFO2 Reference: [087-001]) if b has_participant c at t then c exists at t. (axiom label in BFO2 Reference: [089-001]) if b has_participant c at t then c is a continuant. (axiom label in BFO2 Reference: [088-001]) if b has_participant c at t & c is a generically dependent continuant, then there is some independent continuant that is not a spatial region d, and which is such that c g-depends on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [091-003]) if b has_participant c at t then b is an occurrent. (axiom label in BFO2 Reference: [087-001]) (forall (x y t) (if (hasParticipantAt x y t) (existsAt y t))) // axiom label in BFO2 CLIF: [089-001] (forall (x y t) (if (hasParticipantAt x y t) (Continuant y))) // axiom label in BFO2 CLIF: [088-001] (forall (x y t) (if (and (hasParticipantAt x y t) (SpecificallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t) (specificallyDependsOnAt y z t))))) // axiom label in BFO2 CLIF: [090-003] if b has_participant c at t then c is a continuant. (axiom label in BFO2 Reference: [088-001]) (forall (x y t) (if (and (hasParticipantAt x y t) (GenericallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (genericallyDependsOn y z t) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [091-003] if b has_participant c at t then c exists at t. (axiom label in BFO2 Reference: [089-001]) if b has_participant c at t & c is a specifically dependent continuant, then there is some independent continuant that is not a spatial region d, c s-depends_on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [090-003]) (forall (x y t) (if (hasParticipantAt x y t) (Occurrent x))) // axiom label in BFO2 CLIF: [087-001] has_participant is an instance-level relation between a process, a continuant, and a temporal region at which the continuant participates in some way in the process. (axiom label in BFO2 Reference: [086-003]) concretized by at some time [copied from inverse property 'concretizes at some time'] b concretizes c at t means: b is a specifically dependent continuant & c is a generically dependent continuant & for some independent continuant that is not a spatial region d, b s-depends_on d at t & c g-depends on d at t & if c migrates from bearer d to another bearer e than a copy of b will be created in e. (axiom label in BFO2 Reference: [075-002]) [copied from inverse property 'concretizes at some time'] You may concretize a recipe that you find in a cookbook by turning it into a plan which exists as a realizable dependent continuant in your head. concretized-by_st [copied from inverse property 'concretizes at some time'] you may concretize a poem as a pattern of memory traces in your head [copied from inverse property 'concretizes at some time'] You may concretize a piece of software by installing it in your computer [copied from inverse property 'concretizes at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'concretizes at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'concretizes@en'(x,y,t) concretizes at some time Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'concretizes at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'concretizes@en'(x,y,t) concretizes_st (forall (x y t) (if (genericallyDependsOnAt x y t) (exists (z) (and (concretizesAt z x t) (specificallyDependsOnAt z y t))))) // axiom label in BFO2 CLIF: [076-001] concretizesAt (forall (x y t) (if (concretizesAt x y t) (and (SpecificallyDependentContinuant x) (GenericallyDependentContinuant y) (exists (z) (and (IndependentContinuant z) (specificallyDependsOnAt x z t) (genericallyDependsOnAt y z t)))))) // axiom label in BFO2 CLIF: [075-002] You may concretize a piece of software by installing it in your computer You may concretize a recipe that you find in a cookbook by turning it into a plan which exists as a realizable dependent continuant in your head. b concretizes c at t means: b is a specifically dependent continuant & c is a generically dependent continuant & for some independent continuant that is not a spatial region d, b s-depends_on d at t & c g-depends on d at t & if c migrates from bearer d to another bearer e than a copy of b will be created in e. (axiom label in BFO2 Reference: [075-002]) if b g-depends on c at some time t, then there is some d, such that d concretizes b at t and d s-depends_on c at t. (axiom label in BFO2 Reference: [076-001]) you may concretize a poem as a pattern of memory traces in your head (forall (x y t) (if (concretizesAt x y t) (and (SpecificallyDependentContinuant x) (GenericallyDependentContinuant y) (exists (z) (and (IndependentContinuant z) (specificallyDependsOnAt x z t) (genericallyDependsOnAt y z t)))))) // axiom label in BFO2 CLIF: [075-002] if b g-depends on c at some time t, then there is some d, such that d concretizes b at t and d s-depends_on c at t. (axiom label in BFO2 Reference: [076-001]) (forall (x y t) (if (genericallyDependsOnAt x y t) (exists (z) (and (concretizesAt z x t) (specificallyDependsOnAt z y t))))) // axiom label in BFO2 CLIF: [076-001] b concretizes c at t means: b is a specifically dependent continuant & c is a generically dependent continuant & for some independent continuant that is not a spatial region d, b s-depends_on d at t & c g-depends on d at t & if c migrates from bearer d to another bearer e than a copy of b will be created in e. (axiom label in BFO2 Reference: [075-002]) preceded by An example is: translation preceded_by transcription; aging preceded_by development (not however death preceded_by aging). Where derives_from links classes of continuants, preceded_by links classes of processes. Clearly, however, these two relations are not independent of each other. Thus if cells of type C1 derive_from cells of type C, then any cell division involving an instance of C1 in a given lineage is preceded_by cellular processes involving an instance of C. The assertion P preceded_by P1 tells us something about Ps in general: that is, it tells us something about what happened earlier, given what we know about what happened later. Thus it does not provide information pointing in the opposite direction, concerning instances of P1 in general; that is, that each is such as to be succeeded by some instance of P. Note that an assertion to the effect that P preceded_by P1 is rather weak; it tells us little about the relations between the underlying instances in virtue of which the preceded_by relation obtains. Typically we will be interested in stronger relations, for example in the relation immediately_preceded_by, or in relations which combine preceded_by with a condition to the effect that the corresponding instances of P and P1 share participants, or that their participants are connected by relations of derivation, or (as a first step along the road to a treatment of causality) that the one process in some way affects (for example, initiates or regulates) the other. http://www.obofoundry.org/ro/#OBO_REL:preceded_by is preceded by preceded by preceded_by precedes precedes occurs in occurs in Paraphrase of definition: a relation between a process and an independent continuant, in which the process takes place entirely within the independent continuant b occurs_in c =def b is a process and c is a material entity or immaterial entity& there exists a spatiotemporal region r and b occupies_spatiotemporal_region r.& forall(t) if b exists_at t then c exists_at t & there exist spatial regions s and s’ where & b spatially_projects_onto s at t& c is occupies_spatial_region s’ at t& s is a proper_continuant_part_of s’ at t occurs-in occursIn b occurs_in c =def b is a process and c is a material entity or immaterial entity& there exists a spatiotemporal region r and b occupies_spatiotemporal_region r.& forall(t) if b exists_at t then c exists_at t & there exist spatial regions s and s’ where & b spatially_projects_onto s at t& c is occupies_spatial_region s’ at t& s is a proper_continuant_part_of s’ at t [XXX-001 occurs in occurs_in unfolds in unfolds_in contains process [copied from inverse property 'occurs in'] b occurs_in c =def b is a process and c is a material entity or immaterial entity& there exists a spatiotemporal region r and b occupies_spatiotemporal_region r.& forall(t) if b exists_at t then c exists_at t & there exist spatial regions s and s’ where & b spatially_projects_onto s at t& c is occupies_spatial_region s’ at t& s is a proper_continuant_part_of s’ at t [XXX-001 containsProcess contains-process Paraphrase of definition: a relation between an independent continuant and a process, in which the process takes place entirely within the independent continuant [copied from inverse property 'occurs in'] b occurs_in c =def b is a process and c is a material entity or immaterial entity& there exists a spatiotemporal region r and b occupies_spatiotemporal_region r.& forall(t) if b exists_at t then c exists_at t & there exist spatial regions s and s’ where & b spatially_projects_onto s at t& c is occupies_spatial_region s’ at t& s is a proper_continuant_part_of s’ at t site of begins to exist during begins to exist during begins_to_exist_during specifically depends on at all times (forall (x y t) (if (specificallyDependsOnAt x y t) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [136-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'specifically depends on at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'specifically depends on@en(x,y,t)'. (forall (x y t) (if (and (Occurrent x) (IndependentContinuant y) (specificallyDependsOnAt x y t)) (forall (t_1) (if (existsAt x t_1) (specificallyDependsOnAt x y t_1))))) // axiom label in BFO2 CLIF: [015-002] (forall (x) (if (exists (y t) (specificallyDependsOnAt x y t)) (not (MaterialEntity x)))) // axiom label in BFO2 CLIF: [052-001] BFO2 Reference: specifically dependent continuant\; process; process boundary s-depends-on_at (forall (x y z t) (if (and (specificallyDependsOnAt x y t) (specificallyDependsOnAt y z t)) (specificallyDependsOnAt x z t))) // axiom label in BFO2 CLIF: [054-002] (forall (x y t) (if (and (Entity x) (or (continuantPartOfAt y x t) (continuantPartOfAt x y t) (occurrentPartOf x y) (occurrentPartOf y x))) (not (specificallyDependsOnAt x y t)))) // axiom label in BFO2 CLIF: [013-002] A pain s-depends_on the organism that is experiencing the pain BFO 2 Reference: An entity – for example an act of communication or a game of football – can s-depends_on more than one entity. Complex phenomena for example in the psychological and social realms (such as inferring, commanding and requesting) or in the realm of multi-organismal biological processes (such as infection and resistance), will involve multiple families of dependence relations, involving both continuants and occurrents [1, 4, 28 BFO 2 Reference: S-dependence is just one type of dependence among many; it is what, in the literature, is referred to as ‘existential dependence’ [87, 46, 65, 20 BFO 2 Reference: the relation of s-depends_on does not in every case require simultaneous existence of its relata. Note the difference between such cases and the cases of continuant universals defined historically: the act of answering depends existentially on the prior act of questioning; the human being who was baptized or who answered a question does not himself depend existentially on the prior act of baptism or answering. He would still exist even if these acts had never taken place. If occurrent b s-depends_on some independent continuant c at t, then b s-depends_on c at every time at which b exists. (axiom label in BFO2 Reference: [015-002]) a gait s-depends_on the walking object. (All at some specific time.) if b s-depends_on c at t & c s-depends_on d at t then b s-depends_on d at t. (axiom label in BFO2 Reference: [054-002]) one-sided s-dependence of a dependent continuant on an independent continuant: an instance of headache s-depends_on some head one-sided s-dependence of a dependent continuant on an independent continuant: an instance of temperature s-depends_on some organism one-sided s-dependence of a process on something: a process of cell death s-depends_on a cell specificallyDependsOn If b is s-depends_on something at some time, then b is not a material entity. (axiom label in BFO2 Reference: [052-001]) If b s-depends_on something at t, then there is some c, which is an independent continuant and not a spatial region, such that b s-depends_on c at t. (axiom label in BFO2 Reference: [136-001]) To say that b s-depends_on a at t is to say that b and c do not share common parts & b is of its nature such that it cannot exist unless c exists & b is not a boundary of c and b is not a site of which c is the host [64 a shape s-depends_on the shaped object an entity does not s-depend_on any of its (continuant or occurrent) parts or on anything it is part of. (axiom label in BFO2 Reference: [013-002]) one-sided s-dependence of a process on something: an instance of seeing (a relational process) s-depends_on some organism and on some seen entity, which may be an occurrent or a continuant one-sided s-dependence of one occurrent on another: a process of answering a question is dependent on a prior process of asking a question one-sided s-dependence of one occurrent on another: a process of obeying a command is dependent on a prior process of issuing a command one-sided s-dependence of one occurrent on multiple independent continuants: a relational process of hitting a ball with a cricket bat one-sided s-dependence of one occurrent on multiple independent continuants: a relational process of paying cash to a merchant in exchange for a bag of figs reciprocal s-dependence between occurrents: a process of buying and the associated process of selling reciprocal s-dependence between occurrents: a process of increasing the volume of a portion of gas while temperature remains constant and the associated process of decreasing the pressure exerted by the gas reciprocal s-dependence between occurrents: in a game of chess the process of playing with the white pieces is mutually dependent on the process of playing with the black pieces the one-sided dependence of an occurrent on an independent continuant: football match on the players, the ground, the ball the one-sided dependence of an occurrent on an independent continuant: handwave on a hand the three-sided reciprocal s-dependence of the hue, saturation and brightness of a color [45 the three-sided reciprocal s-dependence of the pitch, timbre and volume of a tone [45 the two-sided reciprocal s-dependence of the roles of husband and wife [20 If occurrent b s-depends_on some independent continuant c at t, then b s-depends_on c at every time at which b exists. (axiom label in BFO2 Reference: [015-002]) (forall (x y t) (if (and (Occurrent x) (IndependentContinuant y) (specificallyDependsOnAt x y t)) (forall (t_1) (if (existsAt x t_1) (specificallyDependsOnAt x y t_1))))) // axiom label in BFO2 CLIF: [015-002] (forall (x y t) (if (specificallyDependsOnAt x y t) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [136-001] If b s-depends_on something at t, then there is some c, which is an independent continuant and not a spatial region, such that b s-depends_on c at t. (axiom label in BFO2 Reference: [136-001]) (forall (x y z t) (if (and (specificallyDependsOnAt x y t) (specificallyDependsOnAt y z t)) (specificallyDependsOnAt x z t))) // axiom label in BFO2 CLIF: [054-002] an entity does not s-depend_on any of its (continuant or occurrent) parts or on anything it is part of. (axiom label in BFO2 Reference: [013-002]) (forall (x y t) (if (and (Entity x) (or (continuantPartOfAt y x t) (continuantPartOfAt x y t) (occurrentPartOf x y) (occurrentPartOf y x))) (not (specificallyDependsOnAt x y t)))) // axiom label in BFO2 CLIF: [013-002] if b s-depends_on c at t & c s-depends_on d at t then b s-depends_on d at t. (axiom label in BFO2 Reference: [054-002]) If b is s-depends_on something at some time, then b is not a material entity. (axiom label in BFO2 Reference: [052-001]) (forall (x) (if (exists (y t) (specificallyDependsOnAt x y t)) (not (MaterialEntity x)))) // axiom label in BFO2 CLIF: [052-001] function of at all times (iff (functionOf a b t) (and (Function a) (inheresInAt a b t))) // axiom label in BFO2 CLIF: [067-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'function of at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'function of@en(x,y,t)'. f-of_at functionOfAt a function_of b at t =Def. a is a function and a inheres_in b at t. (axiom label in BFO2 Reference: [067-001]) a function_of b at t =Def. a is a function and a inheres_in b at t. (axiom label in BFO2 Reference: [067-001]) (iff (functionOf a b t) (and (Function a) (inheresInAt a b t))) // axiom label in BFO2 CLIF: [067-001] quality of at all times qualityOfAt q-of_at Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'quality of at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'quality of@en(x,y,t)'. (iff (qualityOfAt a b t) (and (Quality a) (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))) // axiom label in BFO2 CLIF: [056-002] b quality_of c at t = Def. b is a quality & c is an independent continuant that is not a spatial region & b s-depends_on c at t. (axiom label in BFO2 Reference: [056-002]) b quality_of c at t = Def. b is a quality & c is an independent continuant that is not a spatial region & b s-depends_on c at t. (axiom label in BFO2 Reference: [056-002]) (iff (qualityOfAt a b t) (and (Quality a) (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))) // axiom label in BFO2 CLIF: [056-002] role of at all times r-of_at Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'role of at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'role of@en(x,y,t)'. roleOfAt (iff (roleOfAt a b t) (and (Role a) (inheresInAt a b t))) // axiom label in BFO2 CLIF: [065-001] a role_of b at t =Def. a is a role and a inheres_in b at t. (axiom label in BFO2 Reference: [065-001]) (iff (roleOfAt a b t) (and (Role a) (inheresInAt a b t))) // axiom label in BFO2 CLIF: [065-001] a role_of b at t =Def. a is a role and a inheres_in b at t. (axiom label in BFO2 Reference: [065-001]) located in at all times locatedInAt BFO2 Reference: independent continuant (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (locatedInAt x y t) (continuantPartOfAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [049-001] (iff (locatedInAt a b t) (and (IndependentContinuant a) (IndependentContinuant b) (exists (r_1 r_2) (and (occupiesSpatialRegionAt a r_1 t) (occupiesSpatialRegionAt b r_2 t) (continuantPartOfAt r_1 r_2 t))))) // axiom label in BFO2 CLIF: [045-001] located-in_at (forall (x y z t) (if (and (locatedInAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [046-001] (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (continuantPartOfAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [048-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'located in at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'located in@en(x,y,t)'. Located_in is transitive. (axiom label in BFO2 Reference: [046-001]) Mary located_in Salzburg b located_in c at t = Def. b and c are independent continuants, and the region at which b is located at t is a (proper or improper) continuant_part_of the region at which c is located at t. (axiom label in BFO2 Reference: [045-001]) for all independent continuants b, c, and d: if b continuant_part_of c at t & c located_in d at t, then b located_in d at t. (axiom label in BFO2 Reference: [048-001]) for all independent continuants b, c, and d: if b located_in c at t & c continuant_part_of d at t, then b located_in d at t. (axiom label in BFO2 Reference: [049-001]) the Empire State Building located_in New York. this portion of cocaine located_in this portion of blood this stem cell located_in this portion of bone marrow your arm located_in your body (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (continuantPartOfAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [048-001] Located_in is transitive. (axiom label in BFO2 Reference: [046-001]) (forall (x y z t) (if (and (locatedInAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [046-001] for all independent continuants b, c, and d: if b located_in c at t & c continuant_part_of d at t, then b located_in d at t. (axiom label in BFO2 Reference: [049-001]) (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (locatedInAt x y t) (continuantPartOfAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [049-001] b located_in c at t = Def. b and c are independent continuants, and the region at which b is located at t is a (proper or improper) continuant_part_of the region at which c is located at t. (axiom label in BFO2 Reference: [045-001]) (iff (locatedInAt a b t) (and (IndependentContinuant a) (IndependentContinuant b) (exists (r_1 r_2) (and (occupiesSpatialRegionAt a r_1 t) (occupiesSpatialRegionAt b r_2 t) (continuantPartOfAt r_1 r_2 t))))) // axiom label in BFO2 CLIF: [045-001] for all independent continuants b, c, and d: if b continuant_part_of c at t & c located_in d at t, then b located_in d at t. (axiom label in BFO2 Reference: [048-001]) occupies spatial region at some time located-at-r_st (forall (x y r_1 t) (if (and (occupiesSpatialRegionAt x r_1 t) (continuantPartOfAt y x t)) (exists (r_2) (and (continuantPartOfAt r_2 r_1 t) (occupiesSpatialRegionAt y r_2 t))))) // axiom label in BFO2 CLIF: [043-001] BFO2 Reference: independent continuant Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'occupies spatial region at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'occupies spatial region@en'(x,y,t) (forall (x r t) (if (occupiesSpatialRegionAt x r t) (and (SpatialRegion r) (IndependentContinuant x)))) // axiom label in BFO2 CLIF: [041-002] BFO2 Reference: spatial region (forall (r t) (if (Region r) (occupiesSpatialRegionAt r r t))) // axiom label in BFO2 CLIF: [042-002] b occupies_spatial_region r at t means that r is a spatial region in which independent continuant b is exactly located (axiom label in BFO2 Reference: [041-002]) every region r is occupies_spatial_region r at all times. (axiom label in BFO2 Reference: [042-002]) if b occupies_spatial_region r at t & b continuant_part_of b at t, then there is some r which is continuant_part_of r at t such that b occupies_spatial_region r at t. (axiom label in BFO2 Reference: [043-001]) occupiesSpatialRegionAt (forall (r t) (if (Region r) (occupiesSpatialRegionAt r r t))) // axiom label in BFO2 CLIF: [042-002] every region r is occupies_spatial_region r at all times. (axiom label in BFO2 Reference: [042-002]) (forall (x r t) (if (occupiesSpatialRegionAt x r t) (and (SpatialRegion r) (IndependentContinuant x)))) // axiom label in BFO2 CLIF: [041-002] (forall (x y r_1 t) (if (and (occupiesSpatialRegionAt x r_1 t) (continuantPartOfAt y x t)) (exists (r_2) (and (continuantPartOfAt r_2 r_1 t) (occupiesSpatialRegionAt y r_2 t))))) // axiom label in BFO2 CLIF: [043-001] if b occupies_spatial_region r at t & b continuant_part_of b at t, then there is some r which is continuant_part_of r at t such that b occupies_spatial_region r at t. (axiom label in BFO2 Reference: [043-001]) b occupies_spatial_region r at t means that r is a spatial region in which independent continuant b is exactly located (axiom label in BFO2 Reference: [041-002]) generically depends on at some time (forall (x y) (if (exists (t) (genericallyDependsOnAt x y t)) (forall (t_1) (if (existsAt x t_1) (exists (z) (genericallyDependsOnAt x z t_1)))))) // axiom label in BFO2 CLIF: [073-001] g-depends-on_st Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'generically depends on at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'generically depends on@en'(x,y,t) BFO2 Reference: independent continuant BFO2 Reference: generically dependent continuant b g-depends on c at t1 means: b exists at t1 and c exists at t1 & for some type B it holds that (c instantiates B at t1) & necessarily, for all t (if b exists at t then some instance_of B exists at t) & not (b s-depends_on c at t1). (axiom label in BFO2 Reference: [072-002]) genericallyDependsOn if b g-depends_on c at some time t, then b g-depends_on something at all times at which b exists. (axiom label in BFO2 Reference: [073-001]) (forall (x y) (if (exists (t) (genericallyDependsOnAt x y t)) (forall (t_1) (if (existsAt x t_1) (exists (z) (genericallyDependsOnAt x z t_1)))))) // axiom label in BFO2 CLIF: [073-001] b g-depends on c at t1 means: b exists at t1 and c exists at t1 & for some type B it holds that (c instantiates B at t1) & necessarily, for all t (if b exists at t then some instance_of B exists at t) & not (b s-depends_on c at t1). (axiom label in BFO2 Reference: [072-002]) if b g-depends_on c at some time t, then b g-depends_on something at all times at which b exists. (axiom label in BFO2 Reference: [073-001]) has function at some time has-f_st (iff (hasFunctionAt a b t) (functionOf b a t)) // axiom label in BFO2 CLIF: [070-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has function at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has function@en'(x,y,t) a has_function b at t =Def. b function_of a at t. (axiom label in BFO2 Reference: [070-001]) hasFunctionAt (iff (hasFunctionAt a b t) (functionOf b a t)) // axiom label in BFO2 CLIF: [070-001] a has_function b at t =Def. b function_of a at t. (axiom label in BFO2 Reference: [070-001]) has quality at some time has-q_st has role at some time hasRoleAt has-r_st Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has role at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has role@en'(x,y,t) (iff (hasRoleAt a b t) (roleOfAt b a t)) // axiom label in BFO2 CLIF: [068-001] a has_role b at t =Def. b role_of a at t. (axiom label in BFO2 Reference: [068-001]) a has_role b at t =Def. b role_of a at t. (axiom label in BFO2 Reference: [068-001]) (iff (hasRoleAt a b t) (roleOfAt b a t)) // axiom label in BFO2 CLIF: [068-001] has generic dependent at some time [copied from inverse property 'generically depends on at some time'] BFO2 Reference: independent continuant [copied from inverse property 'generically depends on at some time'] BFO2 Reference: generically dependent continuant [copied from inverse property 'generically depends on at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'generically depends on at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'generically depends on@en'(x,y,t) [copied from inverse property 'generically depends on at some time'] b g-depends on c at t1 means: b exists at t1 and c exists at t1 & for some type B it holds that (c instantiates B at t1) & necessarily, for all t (if b exists at t then some instance_of B exists at t) & not (b s-depends_on c at t1). (axiom label in BFO2 Reference: [072-002]) has-g-dep_st disposition of at all times d-of_at Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'disposition of at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'disposition of@en(x,y,t)'. (iff (dispositionOf a b t) (and (Disposition a) (inheresInAt a b t))) // axiom label in BFO2 CLIF: [066-001] a disposition_of b at t =Def. a is a disposition and a inheres_in b at t. (axiom label in BFO2 Reference: [066-001]) dispositionOfAt a disposition_of b at t =Def. a is a disposition and a inheres_in b at t. (axiom label in BFO2 Reference: [066-001]) (iff (dispositionOf a b t) (and (Disposition a) (inheresInAt a b t))) // axiom label in BFO2 CLIF: [066-001] exists at BFO2 Reference: entity BFO2 Reference: temporal region b exists_at t means: b is an entity which exists at some temporal region t. (axiom label in BFO2 Reference: [118-002]) existsAt exists-at b exists_at t means: b is an entity which exists at some temporal region t. (axiom label in BFO2 Reference: [118-002]) has continuant part at all times (iff (hasContinuantPartAt a b t) (continuantPartOfAt b a t)) // axiom label in BFO2 CLIF: [006-001] [copied from inverse property 'part of continuant at all times that whole exists'] This is a binary version of a ternary time-indexed, instance level, relation. Unlike the rest of the temporalized relations which temporally quantify over existence of the subject of the relation, this relation temporally quantifies over the existence of the object of the relation. The relation is provided tentatively, to assess whether the GO needs such a relation. It is inverse of 'has continuant part at all times' [copied from inverse property 'part of continuant at all times that whole exists'] forall(t) exists_at(y,t) -> exists_at(x,t) and 'part of continuant'(x,y,t) Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has continuant part at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has continuant part@en(x,y,t)'. hasContinuantPartAt b has_continuant_part c at t = Def. c continuant_part_of b at t. (axiom label in BFO2 Reference: [006-001]) c-has-part_at b has_continuant_part c at t = Def. c continuant_part_of b at t. (axiom label in BFO2 Reference: [006-001]) (iff (hasContinuantPartAt a b t) (continuantPartOfAt b a t)) // axiom label in BFO2 CLIF: [006-001] has proper continuant part at all times hasProperContinuantPartAt Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has proper continuant part at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has proper continuant part@en(x,y,t)'. c-has-ppart_at b has_proper_continuant_part c at t = Def. c proper_continuant_part_of b at t. [XXX-001 has disposition at some time hasDispositionAt has-d_st (iff (hasDispositionAt a b t) (dispositionOf b a t)) // axiom label in BFO2 CLIF: [069-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has disposition at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has disposition@en'(x,y,t) a has_disposition b at t =Def. b disposition_of a at t. (axiom label in BFO2 Reference: [069-001]) (iff (hasDispositionAt a b t) (dispositionOf b a t)) // axiom label in BFO2 CLIF: [069-001] a has_disposition b at t =Def. b disposition_of a at t. (axiom label in BFO2 Reference: [069-001]) has material basis at all times Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has material basis at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has material basis@en(x,y,t)'. has-material-basis_at b has_material_basis c at t means: b is a disposition & c is a material entity & there is some d bearer_of b at t& c continuant_part_of d at t& d has_disposition b at t because c continuant_part_of d at t. (axiom label in BFO2 Reference: [071-002]) hasMaterialBasisAt (forall (x y t) (if (hasMaterialBasisAt x y t) (and (Disposition x) (MaterialEntity y) (exists (z) (and (bearerOfAt z x t) (continuantPartOfAt y z t) (exists (w) (and (Disposition w) (if (hasDisposition z w) (continuantPartOfAt y z t))))))))) // axiom label in BFO2 CLIF: [071-002] the material basis of John’s disposition to cough is the viral infection in John’s upper respiratory tract the material basis of the disposition to wear unevenly of John’s tires is the worn suspension of his car. (forall (x y t) (if (hasMaterialBasisAt x y t) (and (Disposition x) (MaterialEntity y) (exists (z) (and (bearerOfAt z x t) (continuantPartOfAt y z t) (exists (w) (and (Disposition w) (if (hasDisposition z w) (continuantPartOfAt y z t))))))))) // axiom label in BFO2 CLIF: [071-002] b has_material_basis c at t means: b is a disposition & c is a material entity & there is some d bearer_of b at t& c continuant_part_of d at t& d has_disposition b at t because c continuant_part_of d at t. (axiom label in BFO2 Reference: [071-002]) has member part at some time [copied from inverse property 'member part of at some time'] each piece in a chess set is a member part of the chess set; each Beatle in the collection called The Beatles is a member part of The Beatles. [copied from inverse property 'member part of at some time'] each tree in a forest is a member_part of the forest [copied from inverse property 'member part of at some time'] b member_part_of c at t =Def. b is an object & there is at t a mutually exhaustive and pairwise disjoint partition of c into objects x1, …, xn (for some n &gt; 1) with b = xi for some 1 ? i ? n. (axiom label in BFO2 Reference: [026-004]) [copied from inverse property 'member part of at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'member part of at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'member part of@en'(x,y,t) [copied from inverse property 'member part of at some time'] BFO2 Reference: object aggregate has-member-part_st [copied from inverse property 'member part of at some time'] BFO2 Reference: object has occurrent part [copied from inverse property 'part of occurrent'] BFO 2 Reference: a (continuant or occurrent) part of itself. We appreciate that this is counterintuitive for some users, since it implies for example that President Obama is a part of himself. However it brings benefits in simplifying the logical formalism, and it captures an important feature of identity, namely that it is the limit case of mereological inclusion. [copied from inverse property 'part of occurrent'] b occurrent_part_of c =Def. b is a part of c & b and c are occurrents. (axiom label in BFO2 Reference: [003-002]) [copied from inverse property 'part of occurrent'] Mary’s 5th birthday occurrent_part_of Mary’s life [copied from inverse property 'part of occurrent'] The process of a footballer’s heart beating once is an occurrent part but not a temporal_part of a game of football. o-has-part (iff (hasOccurrentPart a b) (occurrentPartOf b a)) // axiom label in BFO2 CLIF: [007-001] [copied from inverse property 'part of occurrent'] BFO2 Reference: occurrent hasOccurrentPart [copied from inverse property 'part of occurrent'] the first set of the tennis match occurrent_part_of the tennis match. b has_occurrent_part c = Def. c occurrent_part_of b. (axiom label in BFO2 Reference: [007-001]) (iff (hasOccurrentPart a b) (occurrentPartOf b a)) // axiom label in BFO2 CLIF: [007-001] b has_occurrent_part c = Def. c occurrent_part_of b. (axiom label in BFO2 Reference: [007-001]) has proper occurrent part o-has-ppart hasProperOccurrentPart [copied from inverse property 'proper part of occurrent'] b proper_occurrent_part_of c =Def. b occurrent_part_of c & b and c are not identical. (axiom label in BFO2 Reference: [005-001]) b has_proper_occurrent_part c = Def. c proper_occurrent_part_of b. [XXX-001 has profile has-profile has temporal part [copied from inverse property 'temporal part of'] the 4th year of your life is a temporal part of your life\. The first quarter of a game of football is a temporal part of the whole game\. The process of your heart beating from 4pm to 5pm today is a temporal part of the entire process of your heart beating.\ The 4th year of your life is a temporal part of your life [copied from inverse property 'temporal part of'] the process boundary which separates the 3rd and 4th years of your life. [copied from inverse property 'temporal part of'] b proper_temporal_part_of c =Def. b temporal_part_of c & not (b = c). (axiom label in BFO2 Reference: [116-001]) [copied from inverse property 'temporal part of'] b temporal_part_of c =Def.b occurrent_part_of c & & for some temporal region t, b occupies_temporal_region t & for all occurrents d, t (if d occupies_temporal_region t & t? occurrent_part_of t then (d occurrent_part_of a iff d occurrent_part_of b)). (axiom label in BFO2 Reference: [078-003]) [copied from inverse property 'temporal part of'] your heart beating from 4pm to 5pm today is a temporal part of the process of your heart beating has-t-part has spatial occupant at some time r-location-of_st [copied from inverse property 'occupies spatial region at some time'] b occupies_spatial_region r at t means that r is a spatial region in which independent continuant b is exactly located (axiom label in BFO2 Reference: [041-002]) [copied from inverse property 'occupies spatial region at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'occupies spatial region at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'occupies spatial region@en'(x,y,t) [copied from inverse property 'occupies spatial region at some time'] BFO2 Reference: independent continuant [copied from inverse property 'occupies spatial region at some time'] BFO2 Reference: spatial region has location at some time [copied from inverse property 'located in at some time'] Mary located_in Salzburg [copied from inverse property 'located in at some time'] the Empire State Building located_in New York. [copied from inverse property 'located in at some time'] b located_in c at t = Def. b and c are independent continuants, and the region at which b is located at t is a (proper or improper) continuant_part_of the region at which c is located at t. (axiom label in BFO2 Reference: [045-001]) [copied from inverse property 'located in at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'located in at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'located in@en'(x,y,t) [copied from inverse property 'located in at some time'] your arm located_in your body [copied from inverse property 'located in at some time'] this portion of cocaine located_in this portion of blood has-location_st [copied from inverse property 'located in at some time'] BFO2 Reference: independent continuant [copied from inverse property 'located in at some time'] this stem cell located_in this portion of bone marrow has specific dependent at some time [copied from inverse property 'specifically depends on at some time'] a shape s-depends_on the shaped object has-s-dep_st [copied from inverse property 'specifically depends on at some time'] To say that b s-depends_on a at t is to say that b and c do not share common parts & b is of its nature such that it cannot exist unless c exists & b is not a boundary of c and b is not a site of which c is the host [64 [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of a process on something: an instance of seeing (a relational process) s-depends_on some organism and on some seen entity, which may be an occurrent or a continuant [copied from inverse property 'specifically depends on at some time'] the one-sided dependence of an occurrent on an independent continuant: football match on the players, the ground, the ball [copied from inverse property 'specifically depends on at some time'] a gait s-depends_on the walking object. (All at some specific time.) [copied from inverse property 'specifically depends on at some time'] A pain s-depends_on the organism that is experiencing the pain [copied from inverse property 'specifically depends on at some time'] BFO 2 Reference: the relation of s-depends_on does not in every case require simultaneous existence of its relata. Note the difference between such cases and the cases of continuant universals defined historically: the act of answering depends existentially on the prior act of questioning; the human being who was baptized or who answered a question does not himself depend existentially on the prior act of baptism or answering. He would still exist even if these acts had never taken place. [copied from inverse property 'specifically depends on at some time'] the two-sided reciprocal s-dependence of the roles of husband and wife [20 [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of one occurrent on multiple independent continuants: a relational process of paying cash to a merchant in exchange for a bag of figs [copied from inverse property 'specifically depends on at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'specifically depends on at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'specifically depends on@en'(x,y,t) [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of one occurrent on multiple independent continuants: a relational process of hitting a ball with a cricket bat [copied from inverse property 'specifically depends on at some time'] the one-sided dependence of an occurrent on an independent continuant: handwave on a hand [copied from inverse property 'specifically depends on at some time'] reciprocal s-dependence between occurrents: in a game of chess the process of playing with the white pieces is mutually dependent on the process of playing with the black pieces [copied from inverse property 'specifically depends on at some time'] BFO2 Reference: specifically dependent continuant\; process; process boundary [copied from inverse property 'specifically depends on at some time'] the three-sided reciprocal s-dependence of the hue, saturation and brightness of a color [45 [copied from inverse property 'specifically depends on at some time'] reciprocal s-dependence between occurrents: a process of buying and the associated process of selling [copied from inverse property 'specifically depends on at some time'] the three-sided reciprocal s-dependence of the pitch, timbre and volume of a tone [45 [copied from inverse property 'specifically depends on at some time'] reciprocal s-dependence between occurrents: a process of increasing the volume of a portion of gas while temperature remains constant and the associated process of decreasing the pressure exerted by the gas [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of a dependent continuant on an independent continuant: an instance of temperature s-depends_on some organism [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of one occurrent on another: a process of obeying a command is dependent on a prior process of issuing a command [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of a process on something: a process of cell death s-depends_on a cell [copied from inverse property 'specifically depends on at some time'] BFO 2 Reference: S-dependence is just one type of dependence among many; it is what, in the literature, is referred to as ‘existential dependence’ [87, 46, 65, 20 [copied from inverse property 'specifically depends on at some time'] BFO 2 Reference: An entity – for example an act of communication or a game of football – can s-depends_on more than one entity. Complex phenomena for example in the psychological and social realms (such as inferring, commanding and requesting) or in the realm of multi-organismal biological processes (such as infection and resistance), will involve multiple families of dependence relations, involving both continuants and occurrents [1, 4, 28 [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of a dependent continuant on an independent continuant: an instance of headache s-depends_on some head [copied from inverse property 'specifically depends on at some time'] one-sided s-dependence of one occurrent on another: a process of answering a question is dependent on a prior process of asking a question has spatiotemporal occupant [copied from inverse property 'occupies spatiotemporal region'] BFO 2 Reference: The occupies_spatiotemporal_region and occupies_temporal_region relations are the counterpart, on the occurrent side, of the relation occupies_spatial_region. occupied-by [copied from inverse property 'occupies spatiotemporal region'] p occupies_spatiotemporal_region s. This is a primitive relation between an occurrent p and the spatiotemporal region s which is its spatiotemporal extent. (axiom label in BFO2 Reference: [082-003]) material basis of at some time material-basis-of_st member part of at some time member-part-of_st memberPartOfAt BFO2 Reference: object BFO2 Reference: object aggregate (forall (x y t) (if (memberPartOfAt x y t) (continuantPartOfAt x y t))) // axiom label in BFO2 CLIF: [104-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'member part of at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'member part of@en'(x,y,t) b member_part_of c at t =Def. b is an object & there is at t a mutually exhaustive and pairwise disjoint partition of c into objects x1, …, xn (for some n &gt; 1) with b = xi for some 1 ? i ? n. (axiom label in BFO2 Reference: [026-004]) each piece in a chess set is a member part of the chess set; each Beatle in the collection called The Beatles is a member part of The Beatles. each tree in a forest is a member_part of the forest if b member_part_of c at t then b continuant_part_of c at t. (axiom label in BFO2 Reference: [104-001]) b member_part_of c at t =Def. b is an object & there is at t a mutually exhaustive and pairwise disjoint partition of c into objects x1, …, xn (for some n &gt; 1) with b = xi for some 1 ? i ? n. (axiom label in BFO2 Reference: [026-004]) if b member_part_of c at t then b continuant_part_of c at t. (axiom label in BFO2 Reference: [104-001]) (forall (x y t) (if (memberPartOfAt x y t) (continuantPartOfAt x y t))) // axiom label in BFO2 CLIF: [104-001] occupies spatiotemporal region occupiesSpatiotemporalRegion BFO 2 Reference: The occupies_spatiotemporal_region and occupies_temporal_region relations are the counterpart, on the occurrent side, of the relation occupies_spatial_region. occupies p occupies_spatiotemporal_region s. This is a primitive relation between an occurrent p and the spatiotemporal region s which is its spatiotemporal extent. (axiom label in BFO2 Reference: [082-003]) p occupies_spatiotemporal_region s. This is a primitive relation between an occurrent p and the spatiotemporal region s which is its spatiotemporal extent. (axiom label in BFO2 Reference: [082-003]) part of occurrent BFO2 Reference: occurrent occurrentPartOf o-part-of (forall (x y t) (if (and (occurrentPartOf x y t) (occurrentPartOf y x t)) (= x y))) // axiom label in BFO2 CLIF: [123-001] (forall (x y t) (if (and (occurrentPartOf x y t) (not (= x y))) (exists (z) (and (occurrentPartOf z y t) (not (exists (w) (and (occurrentPartOf w x t) (occurrentPartOf w z t)))))))) // axiom label in BFO2 CLIF: [124-001] [copied from inverse property 'has occurrent part'] b has_occurrent_part c = Def. c occurrent_part_of b. (axiom label in BFO2 Reference: [007-001]) (forall (x) (if (Occurrent x) (occurrentPartOf x x))) // axiom label in BFO2 CLIF: [113-002] (forall (x y z) (if (and (occurrentPartOf x y) (occurrentPartOf y z)) (occurrentPartOf x z))) // axiom label in BFO2 CLIF: [112-001] (forall (x y t) (if (exists (v) (and (occurrentPartOf v x t) (occurrentPartOf v y t))) (exists (z) (forall (u w) (iff (iff (occurrentPartOf w u t) (and (occurrentPartOf w x t) (occurrentPartOf w y t))) (= z u)))))) // axiom label in BFO2 CLIF: [125-001] BFO 2 Reference: a (continuant or occurrent) part of itself. We appreciate that this is counterintuitive for some users, since it implies for example that President Obama is a part of himself. However it brings benefits in simplifying the logical formalism, and it captures an important feature of identity, namely that it is the limit case of mereological inclusion. Mary’s 5th birthday occurrent_part_of Mary’s life The process of a footballer’s heart beating once is an occurrent part but not a temporal_part of a game of football. b occurrent_part_of c =Def. b is a part of c & b and c are occurrents. (axiom label in BFO2 Reference: [003-002]) occurrent_part_of is antisymmetric. (axiom label in BFO2 Reference: [123-001]) occurrent_part_of is reflexive (every occurrent entity is an occurrent_part_of itself). (axiom label in BFO2 Reference: [113-002]) occurrent_part_of is transitive. (axiom label in BFO2 Reference: [112-001]) occurrent_part_of satisfies unique product. (axiom label in BFO2 Reference: [125-001]) occurrent_part_of satisfies weak supplementation. (axiom label in BFO2 Reference: [124-001]) the first set of the tennis match occurrent_part_of the tennis match. (forall (x y t) (if (and (occurrentPartOf x y t) (not (= x y))) (exists (z) (and (occurrentPartOf z y t) (not (exists (w) (and (occurrentPartOf w x t) (occurrentPartOf w z t)))))))) // axiom label in BFO2 CLIF: [124-001] (forall (x y t) (if (exists (v) (and (occurrentPartOf v x t) (occurrentPartOf v y t))) (exists (z) (forall (u w) (iff (iff (occurrentPartOf w u t) (and (occurrentPartOf w x t) (occurrentPartOf w y t))) (= z u)))))) // axiom label in BFO2 CLIF: [125-001] occurrent_part_of is reflexive (every occurrent entity is an occurrent_part_of itself). (axiom label in BFO2 Reference: [113-002]) occurrent_part_of is transitive. (axiom label in BFO2 Reference: [112-001]) (forall (x y z) (if (and (occurrentPartOf x y) (occurrentPartOf y z)) (occurrentPartOf x z))) // axiom label in BFO2 CLIF: [112-001] b occurrent_part_of c =Def. b is a part of c & b and c are occurrents. (axiom label in BFO2 Reference: [003-002]) occurrent_part_of satisfies weak supplementation. (axiom label in BFO2 Reference: [124-001]) (forall (x y t) (if (and (occurrentPartOf x y t) (occurrentPartOf y x t)) (= x y))) // axiom label in BFO2 CLIF: [123-001] (forall (x) (if (Occurrent x) (occurrentPartOf x x))) // axiom label in BFO2 CLIF: [113-002] occurrent_part_of satisfies unique product. (axiom label in BFO2 Reference: [125-001]) occurrent_part_of is antisymmetric. (axiom label in BFO2 Reference: [123-001]) process profile of processProfileOf profile-of proper temporal part of properTemporalPartOf t-ppart-of proper part of continuant at all times properContinuantPartOfAt c-ppart-of_at (iff (properContinuantPartOfAt a b t) (and (continuantPartOfAt a b t) (not (= a b)))) // axiom label in BFO2 CLIF: [004-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'proper part of continuant at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'proper part of continuant@en(x,y,t)'. b proper_continuant_part_of c at t =Def. b continuant_part_of c at t & b and c are not identical. (axiom label in BFO2 Reference: [004-001]) (iff (properContinuantPartOfAt a b t) (and (continuantPartOfAt a b t) (not (= a b)))) // axiom label in BFO2 CLIF: [004-001] b proper_continuant_part_of c at t =Def. b continuant_part_of c at t & b and c are not identical. (axiom label in BFO2 Reference: [004-001]) proper part of occurrent [copied from inverse property 'has proper occurrent part'] b has_proper_occurrent_part c = Def. c proper_occurrent_part_of b. [XXX-001 properOccurrentPartOf o-ppart-of (iff (properOccurrentPartOf a b) (and (occurrentPartOf a b) (not (= a b)))) // axiom label in BFO2 CLIF: [005-001] b proper_occurrent_part_of c =Def. b occurrent_part_of c & b and c are not identical. (axiom label in BFO2 Reference: [005-001]) b proper_occurrent_part_of c =Def. b occurrent_part_of c & b and c are not identical. (axiom label in BFO2 Reference: [005-001]) (iff (properOccurrentPartOf a b) (and (occurrentPartOf a b) (not (= a b)))) // axiom label in BFO2 CLIF: [005-001] temporal part of (iff (properTemporalPartOf a b) (and (temporalPartOf a b) (not (= a b)))) // axiom label in BFO2 CLIF: [116-001] temporalPartOf (forall (x y) (if (properTemporalPartOf x y) (exists (z) (and (properTemporalPartOf z y) (not (exists (w) (and (temporalPartOf w x) (temporalPartOf w z)))))))) // axiom label in BFO2 CLIF: [117-002] t-part-of (iff (temporalPartOf a b) (and (occurrentPartOf a b) (exists (t) (and (TemporalRegion t) (occupiesSpatioTemporalRegion a t))) (forall (c t_1) (if (and (Occurrent c) (occupiesSpatioTemporalRegion c t_1) (occurrentPartOf t_1 r)) (iff (occurrentPartOf c a) (occurrentPartOf c b)))))) // axiom label in BFO2 CLIF: [078-003] b proper_temporal_part_of c =Def. b temporal_part_of c & not (b = c). (axiom label in BFO2 Reference: [116-001]) b temporal_part_of c =Def.b occurrent_part_of c & & for some temporal region t, b occupies_temporal_region t & for all occurrents d, t (if d occupies_temporal_region t & t? occurrent_part_of t then (d occurrent_part_of a iff d occurrent_part_of b)). (axiom label in BFO2 Reference: [078-003]) if b proper_temporal_part_of c, then there is some d which is a proper_temporal_part_of c and which shares no parts with b. (axiom label in BFO2 Reference: [117-002]) the 4th year of your life is a temporal part of your life\. The first quarter of a game of football is a temporal part of the whole game\. The process of your heart beating from 4pm to 5pm today is a temporal part of the entire process of your heart beating.\ The 4th year of your life is a temporal part of your life the process boundary which separates the 3rd and 4th years of your life. your heart beating from 4pm to 5pm today is a temporal part of the process of your heart beating (iff (temporalPartOf a b) (and (occurrentPartOf a b) (exists (t) (and (TemporalRegion t) (occupiesSpatioTemporalRegion a t))) (forall (c t_1) (if (and (Occurrent c) (occupiesSpatioTemporalRegion c t_1) (occurrentPartOf t_1 r)) (iff (occurrentPartOf c a) (occurrentPartOf c b)))))) // axiom label in BFO2 CLIF: [078-003] b temporal_part_of c =Def.b occurrent_part_of c & & for some temporal region t, b occupies_temporal_region t & for all occurrents d, t (if d occupies_temporal_region t & t? occurrent_part_of t then (d occurrent_part_of a iff d occurrent_part_of b)). (axiom label in BFO2 Reference: [078-003]) (forall (x y) (if (properTemporalPartOf x y) (exists (z) (and (properTemporalPartOf z y) (not (exists (w) (and (temporalPartOf w x) (temporalPartOf w z)))))))) // axiom label in BFO2 CLIF: [117-002] (iff (properTemporalPartOf a b) (and (temporalPartOf a b) (not (= a b)))) // axiom label in BFO2 CLIF: [116-001] b proper_temporal_part_of c =Def. b temporal_part_of c & not (b = c). (axiom label in BFO2 Reference: [116-001]) if b proper_temporal_part_of c, then there is some d which is a proper_temporal_part_of c and which shares no parts with b. (axiom label in BFO2 Reference: [117-002]) projects onto spatial region at some time st-projects-onto-s_st spatial projection of spatiotemporal at some time s-projection-of-st_st projects onto temporal region st-projects-onto-t temporal projection of spatiotemporal t-projection-of-st occupies temporal region spans occupiesTemporalRegion p occupies_temporal_region t. This is a primitive relation between an occurrent p and the temporal region t upon which the spatiotemporal region p occupies_spatiotemporal_region projects. (axiom label in BFO2 Reference: [132-001]) p occupies_temporal_region t. This is a primitive relation between an occurrent p and the temporal region t upon which the spatiotemporal region p occupies_spatiotemporal_region projects. (axiom label in BFO2 Reference: [132-001]) has temporal occupant [copied from inverse property 'occupies temporal region'] p occupies_temporal_region t. This is a primitive relation between an occurrent p and the temporal region t upon which the spatiotemporal region p occupies_spatiotemporal_region projects. (axiom label in BFO2 Reference: [132-001]) span-of spanOf during which exists [copied from inverse property 'exists at'] BFO2 Reference: entity during-which-exists [copied from inverse property 'exists at'] BFO2 Reference: temporal region [copied from inverse property 'exists at'] b exists_at t means: b is an entity which exists at some temporal region t. (axiom label in BFO2 Reference: [118-002]) bearer of at all times (iff (bearerOfAt a b t) (and (specificallyDependsOnAt b a t) (IndependentContinuant a) (not (SpatialRegion a)) (existsAt b t))) // axiom label in BFO2 CLIF: [053-004] bearerOfAt BFO2 Reference: independent continuant that is not a spatial region bearer-of_at Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'bearer of at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'bearer of@en(x,y,t)'. BFO2 Reference: specifically dependent continuant b bearer_of c at t =Def. c s-depends_on b at t & b is an independent continuant that is not a spatial region. (axiom label in BFO2 Reference: [053-004]) b bearer_of c at t =Def. c s-depends_on b at t & b is an independent continuant that is not a spatial region. (axiom label in BFO2 Reference: [053-004]) (iff (bearerOfAt a b t) (and (specificallyDependsOnAt b a t) (IndependentContinuant a) (not (SpatialRegion a)) (existsAt b t))) // axiom label in BFO2 CLIF: [053-004] has quality at all times has-q_at has function at all times has-f_at Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has function at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has function@en(x,y,t)'. a has_function b at t =Def. b function_of a at t. (axiom label in BFO2 Reference: [070-001]) hasFunctionAt (iff (hasFunctionAt a b t) (functionOf b a t)) // axiom label in BFO2 CLIF: [070-001] a has_function b at t =Def. b function_of a at t. (axiom label in BFO2 Reference: [070-001]) (iff (hasFunctionAt a b t) (functionOf b a t)) // axiom label in BFO2 CLIF: [070-001] has role at all times hasRoleAt Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has role at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has role@en(x,y,t)'. has-r_at (iff (hasRoleAt a b t) (roleOfAt b a t)) // axiom label in BFO2 CLIF: [068-001] a has_role b at t =Def. b role_of a at t. (axiom label in BFO2 Reference: [068-001]) (iff (hasRoleAt a b t) (roleOfAt b a t)) // axiom label in BFO2 CLIF: [068-001] a has_role b at t =Def. b role_of a at t. (axiom label in BFO2 Reference: [068-001]) has disposition at all times (iff (hasDispositionAt a b t) (dispositionOf b a t)) // axiom label in BFO2 CLIF: [069-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has disposition at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has disposition@en(x,y,t)'. a has_disposition b at t =Def. b disposition_of a at t. (axiom label in BFO2 Reference: [069-001]) hasDispositionAt has-d_at (iff (hasDispositionAt a b t) (dispositionOf b a t)) // axiom label in BFO2 CLIF: [069-001] a has_disposition b at t =Def. b disposition_of a at t. (axiom label in BFO2 Reference: [069-001]) material basis of at all times material-basis-of_at concretizes at all times concretizesAt (forall (x y t) (if (concretizesAt x y t) (and (SpecificallyDependentContinuant x) (GenericallyDependentContinuant y) (exists (z) (and (IndependentContinuant z) (specificallyDependsOnAt x z t) (genericallyDependsOnAt y z t)))))) // axiom label in BFO2 CLIF: [075-002] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'concretizes at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'concretizes@en(x,y,t)'. concretizes_at (forall (x y t) (if (genericallyDependsOnAt x y t) (exists (z) (and (concretizesAt z x t) (specificallyDependsOnAt z y t))))) // axiom label in BFO2 CLIF: [076-001] You may concretize a piece of software by installing it in your computer You may concretize a recipe that you find in a cookbook by turning it into a plan which exists as a realizable dependent continuant in your head. b concretizes c at t means: b is a specifically dependent continuant & c is a generically dependent continuant & for some independent continuant that is not a spatial region d, b s-depends_on d at t & c g-depends on d at t & if c migrates from bearer d to another bearer e than a copy of b will be created in e. (axiom label in BFO2 Reference: [075-002]) if b g-depends on c at some time t, then there is some d, such that d concretizes b at t and d s-depends_on c at t. (axiom label in BFO2 Reference: [076-001]) you may concretize a poem as a pattern of memory traces in your head if b g-depends on c at some time t, then there is some d, such that d concretizes b at t and d s-depends_on c at t. (axiom label in BFO2 Reference: [076-001]) (forall (x y t) (if (concretizesAt x y t) (and (SpecificallyDependentContinuant x) (GenericallyDependentContinuant y) (exists (z) (and (IndependentContinuant z) (specificallyDependsOnAt x z t) (genericallyDependsOnAt y z t)))))) // axiom label in BFO2 CLIF: [075-002] b concretizes c at t means: b is a specifically dependent continuant & c is a generically dependent continuant & for some independent continuant that is not a spatial region d, b s-depends_on d at t & c g-depends on d at t & if c migrates from bearer d to another bearer e than a copy of b will be created in e. (axiom label in BFO2 Reference: [075-002]) (forall (x y t) (if (genericallyDependsOnAt x y t) (exists (z) (and (concretizesAt z x t) (specificallyDependsOnAt z y t))))) // axiom label in BFO2 CLIF: [076-001] concretized by at all times concretized-by_at participates in at all times participates-in_at participatesInAt has participant at all times Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has participant at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has participant@en(x,y,t)'. has-participant_at (forall (x y t) (if (and (hasParticipantAt x y t) (GenericallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (genericallyDependsOn y z t) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [091-003] BFO2 Reference: independent continuant that is not a spatial region, specifically dependent continuant, generically dependent continuant (forall (x y t) (if (hasParticipantAt x y t) (Occurrent x))) // axiom label in BFO2 CLIF: [087-001] (forall (x y t) (if (hasParticipantAt x y t) (Continuant y))) // axiom label in BFO2 CLIF: [088-001] BFO2 Reference: process hasParticipantAt (forall (x y t) (if (and (hasParticipantAt x y t) (SpecificallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t) (specificallyDependsOnAt y z t))))) // axiom label in BFO2 CLIF: [090-003] (forall (x y t) (if (hasParticipantAt x y t) (existsAt y t))) // axiom label in BFO2 CLIF: [089-001] BFO 2 Reference: Spatial regions do not participate in processes. has_participant is an instance-level relation between a process, a continuant, and a temporal region at which the continuant participates in some way in the process. (axiom label in BFO2 Reference: [086-003]) if b has_participant c at t & c is a generically dependent continuant, then there is some independent continuant that is not a spatial region d, and which is such that c g-depends on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [091-003]) if b has_participant c at t & c is a specifically dependent continuant, then there is some independent continuant that is not a spatial region d, c s-depends_on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [090-003]) if b has_participant c at t then b is an occurrent. (axiom label in BFO2 Reference: [087-001]) if b has_participant c at t then c exists at t. (axiom label in BFO2 Reference: [089-001]) if b has_participant c at t then c is a continuant. (axiom label in BFO2 Reference: [088-001]) if b has_participant c at t then c exists at t. (axiom label in BFO2 Reference: [089-001]) if b has_participant c at t & c is a generically dependent continuant, then there is some independent continuant that is not a spatial region d, and which is such that c g-depends on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [091-003]) (forall (x y t) (if (hasParticipantAt x y t) (existsAt y t))) // axiom label in BFO2 CLIF: [089-001] (forall (x y t) (if (and (hasParticipantAt x y t) (GenericallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (genericallyDependsOn y z t) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [091-003] if b has_participant c at t then b is an occurrent. (axiom label in BFO2 Reference: [087-001]) if b has_participant c at t & c is a specifically dependent continuant, then there is some independent continuant that is not a spatial region d, c s-depends_on d at t & b s-depends_on d at t. (axiom label in BFO2 Reference: [090-003]) has_participant is an instance-level relation between a process, a continuant, and a temporal region at which the continuant participates in some way in the process. (axiom label in BFO2 Reference: [086-003]) if b has_participant c at t then c is a continuant. (axiom label in BFO2 Reference: [088-001]) (forall (x y t) (if (hasParticipantAt x y t) (Continuant y))) // axiom label in BFO2 CLIF: [088-001] (forall (x y t) (if (hasParticipantAt x y t) (Occurrent x))) // axiom label in BFO2 CLIF: [087-001] (forall (x y t) (if (and (hasParticipantAt x y t) (SpecificallyDependentContinuant y)) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t) (specificallyDependsOnAt y z t))))) // axiom label in BFO2 CLIF: [090-003] has specific dependent at all times has-s-dep_at specifically depends on at some time s-depends-on_st BFO2 Reference: specifically dependent continuant\; process; process boundary (forall (x) (if (exists (y t) (specificallyDependsOnAt x y t)) (not (MaterialEntity x)))) // axiom label in BFO2 CLIF: [052-001] (forall (x y t) (if (and (Occurrent x) (IndependentContinuant y) (specificallyDependsOnAt x y t)) (forall (t_1) (if (existsAt x t_1) (specificallyDependsOnAt x y t_1))))) // axiom label in BFO2 CLIF: [015-002] BFO 2 Reference: S-dependence is just one type of dependence among many; it is what, in the literature, is referred to as ‘existential dependence’ [87, 46, 65, 20 BFO 2 Reference: the relation of s-depends_on does not in every case require simultaneous existence of its relata. Note the difference between such cases and the cases of continuant universals defined historically: the act of answering depends existentially on the prior act of questioning; the human being who was baptized or who answered a question does not himself depend existentially on the prior act of baptism or answering. He would still exist even if these acts had never taken place. If occurrent b s-depends_on some independent continuant c at t, then b s-depends_on c at every time at which b exists. (axiom label in BFO2 Reference: [015-002]) To say that b s-depends_on a at t is to say that b and c do not share common parts & b is of its nature such that it cannot exist unless c exists & b is not a boundary of c and b is not a site of which c is the host [64 one-sided s-dependence of one occurrent on another: a process of answering a question is dependent on a prior process of asking a question one-sided s-dependence of one occurrent on another: a process of obeying a command is dependent on a prior process of issuing a command one-sided s-dependence of one occurrent on multiple independent continuants: a relational process of paying cash to a merchant in exchange for a bag of figs reciprocal s-dependence between occurrents: a process of buying and the associated process of selling reciprocal s-dependence between occurrents: in a game of chess the process of playing with the white pieces is mutually dependent on the process of playing with the black pieces specificallyDependsOn Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'specifically depends on at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'specifically depends on@en'(x,y,t) (forall (x y t) (if (specificallyDependsOnAt x y t) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [136-001] (forall (x y t) (if (and (Entity x) (or (continuantPartOfAt y x t) (continuantPartOfAt x y t) (occurrentPartOf x y) (occurrentPartOf y x))) (not (specificallyDependsOnAt x y t)))) // axiom label in BFO2 CLIF: [013-002] (forall (x y z t) (if (and (specificallyDependsOnAt x y t) (specificallyDependsOnAt y z t)) (specificallyDependsOnAt x z t))) // axiom label in BFO2 CLIF: [054-002] A pain s-depends_on the organism that is experiencing the pain BFO 2 Reference: An entity – for example an act of communication or a game of football – can s-depends_on more than one entity. Complex phenomena for example in the psychological and social realms (such as inferring, commanding and requesting) or in the realm of multi-organismal biological processes (such as infection and resistance), will involve multiple families of dependence relations, involving both continuants and occurrents [1, 4, 28 If b is s-depends_on something at some time, then b is not a material entity. (axiom label in BFO2 Reference: [052-001]) If b s-depends_on something at t, then there is some c, which is an independent continuant and not a spatial region, such that b s-depends_on c at t. (axiom label in BFO2 Reference: [136-001]) a gait s-depends_on the walking object. (All at some specific time.) a shape s-depends_on the shaped object an entity does not s-depend_on any of its (continuant or occurrent) parts or on anything it is part of. (axiom label in BFO2 Reference: [013-002]) if b s-depends_on c at t & c s-depends_on d at t then b s-depends_on d at t. (axiom label in BFO2 Reference: [054-002]) one-sided s-dependence of a dependent continuant on an independent continuant: an instance of headache s-depends_on some head one-sided s-dependence of a dependent continuant on an independent continuant: an instance of temperature s-depends_on some organism one-sided s-dependence of a process on something: a process of cell death s-depends_on a cell one-sided s-dependence of a process on something: an instance of seeing (a relational process) s-depends_on some organism and on some seen entity, which may be an occurrent or a continuant one-sided s-dependence of one occurrent on multiple independent continuants: a relational process of hitting a ball with a cricket bat reciprocal s-dependence between occurrents: a process of increasing the volume of a portion of gas while temperature remains constant and the associated process of decreasing the pressure exerted by the gas the one-sided dependence of an occurrent on an independent continuant: football match on the players, the ground, the ball the one-sided dependence of an occurrent on an independent continuant: handwave on a hand the three-sided reciprocal s-dependence of the hue, saturation and brightness of a color [45 the three-sided reciprocal s-dependence of the pitch, timbre and volume of a tone [45 the two-sided reciprocal s-dependence of the roles of husband and wife [20 If b is s-depends_on something at some time, then b is not a material entity. (axiom label in BFO2 Reference: [052-001]) (forall (x y z t) (if (and (specificallyDependsOnAt x y t) (specificallyDependsOnAt y z t)) (specificallyDependsOnAt x z t))) // axiom label in BFO2 CLIF: [054-002] (forall (x y t) (if (and (Entity x) (or (continuantPartOfAt y x t) (continuantPartOfAt x y t) (occurrentPartOf x y) (occurrentPartOf y x))) (not (specificallyDependsOnAt x y t)))) // axiom label in BFO2 CLIF: [013-002] (forall (x y t) (if (specificallyDependsOnAt x y t) (exists (z) (and (IndependentContinuant z) (not (SpatialRegion z)) (specificallyDependsOnAt x z t))))) // axiom label in BFO2 CLIF: [136-001] if b s-depends_on c at t & c s-depends_on d at t then b s-depends_on d at t. (axiom label in BFO2 Reference: [054-002]) If b s-depends_on something at t, then there is some c, which is an independent continuant and not a spatial region, such that b s-depends_on c at t. (axiom label in BFO2 Reference: [136-001]) an entity does not s-depend_on any of its (continuant or occurrent) parts or on anything it is part of. (axiom label in BFO2 Reference: [013-002]) (forall (x y t) (if (and (Occurrent x) (IndependentContinuant y) (specificallyDependsOnAt x y t)) (forall (t_1) (if (existsAt x t_1) (specificallyDependsOnAt x y t_1))))) // axiom label in BFO2 CLIF: [015-002] If occurrent b s-depends_on some independent continuant c at t, then b s-depends_on c at every time at which b exists. (axiom label in BFO2 Reference: [015-002]) (forall (x) (if (exists (y t) (specificallyDependsOnAt x y t)) (not (MaterialEntity x)))) // axiom label in BFO2 CLIF: [052-001] has location at all times has-location_at located in at some time (iff (locatedInAt a b t) (and (IndependentContinuant a) (IndependentContinuant b) (exists (r_1 r_2) (and (occupiesSpatialRegionAt a r_1 t) (occupiesSpatialRegionAt b r_2 t) (continuantPartOfAt r_1 r_2 t))))) // axiom label in BFO2 CLIF: [045-001] locatedInAt BFO2 Reference: independent continuant (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (continuantPartOfAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [048-001] located-in_st (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (locatedInAt x y t) (continuantPartOfAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [049-001] (forall (x y z t) (if (and (locatedInAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [046-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'located in at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'located in@en'(x,y,t) Located_in is transitive. (axiom label in BFO2 Reference: [046-001]) Mary located_in Salzburg b located_in c at t = Def. b and c are independent continuants, and the region at which b is located at t is a (proper or improper) continuant_part_of the region at which c is located at t. (axiom label in BFO2 Reference: [045-001]) for all independent continuants b, c, and d: if b continuant_part_of c at t & c located_in d at t, then b located_in d at t. (axiom label in BFO2 Reference: [048-001]) for all independent continuants b, c, and d: if b located_in c at t & c continuant_part_of d at t, then b located_in d at t. (axiom label in BFO2 Reference: [049-001]) the Empire State Building located_in New York. this portion of cocaine located_in this portion of blood this stem cell located_in this portion of bone marrow your arm located_in your body (forall (x y z t) (if (and (locatedInAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [046-001] (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (continuantPartOfAt x y t) (locatedInAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [048-001] (iff (locatedInAt a b t) (and (IndependentContinuant a) (IndependentContinuant b) (exists (r_1 r_2) (and (occupiesSpatialRegionAt a r_1 t) (occupiesSpatialRegionAt b r_2 t) (continuantPartOfAt r_1 r_2 t))))) // axiom label in BFO2 CLIF: [045-001] for all independent continuants b, c, and d: if b located_in c at t & c continuant_part_of d at t, then b located_in d at t. (axiom label in BFO2 Reference: [049-001]) (forall (x y z t) (if (and (IndependentContinuant x) (IndependentContinuant y) (IndependentContinuant z) (locatedInAt x y t) (continuantPartOfAt y z t)) (locatedInAt x z t))) // axiom label in BFO2 CLIF: [049-001] for all independent continuants b, c, and d: if b continuant_part_of c at t & c located_in d at t, then b located_in d at t. (axiom label in BFO2 Reference: [048-001]) Located_in is transitive. (axiom label in BFO2 Reference: [046-001]) b located_in c at t = Def. b and c are independent continuants, and the region at which b is located at t is a (proper or improper) continuant_part_of the region at which c is located at t. (axiom label in BFO2 Reference: [045-001]) has member part at all times has-member-part_at member part of at all times member-part-of_at (forall (x y t) (if (memberPartOfAt x y t) (continuantPartOfAt x y t))) // axiom label in BFO2 CLIF: [104-001] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'member part of at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'member part of@en(x,y,t)'. memberPartOfAt BFO2 Reference: object aggregate BFO2 Reference: object b member_part_of c at t =Def. b is an object & there is at t a mutually exhaustive and pairwise disjoint partition of c into objects x1, …, xn (for some n &gt; 1) with b = xi for some 1 ? i ? n. (axiom label in BFO2 Reference: [026-004]) each piece in a chess set is a member part of the chess set; each Beatle in the collection called The Beatles is a member part of The Beatles. each tree in a forest is a member_part of the forest if b member_part_of c at t then b continuant_part_of c at t. (axiom label in BFO2 Reference: [104-001]) b member_part_of c at t =Def. b is an object & there is at t a mutually exhaustive and pairwise disjoint partition of c into objects x1, …, xn (for some n &gt; 1) with b = xi for some 1 ? i ? n. (axiom label in BFO2 Reference: [026-004]) (forall (x y t) (if (memberPartOfAt x y t) (continuantPartOfAt x y t))) // axiom label in BFO2 CLIF: [104-001] if b member_part_of c at t then b continuant_part_of c at t. (axiom label in BFO2 Reference: [104-001]) has proper continuant part at some time c-has-ppart_st [copied from inverse property 'proper part of continuant at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'proper part of continuant at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'proper part of continuant@en'(x,y,t) Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has proper continuant part at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has proper continuant part@en'(x,y,t) hasProperContinuantPartAt [copied from inverse property 'proper part of continuant at some time'] b proper_continuant_part_of c at t =Def. b continuant_part_of c at t & b and c are not identical. (axiom label in BFO2 Reference: [004-001]) b has_proper_continuant_part c at t = Def. c proper_continuant_part_of b at t. [XXX-001 proper part of continuant at some time [copied from inverse property 'has proper continuant part at some time'] b has_proper_continuant_part c at t = Def. c proper_continuant_part_of b at t. [XXX-001 (iff (properContinuantPartOfAt a b t) (and (continuantPartOfAt a b t) (not (= a b)))) // axiom label in BFO2 CLIF: [004-001] c-ppart-of_st Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'proper part of continuant at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'proper part of continuant@en'(x,y,t) [copied from inverse property 'has proper continuant part at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has proper continuant part at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has proper continuant part@en'(x,y,t) b proper_continuant_part_of c at t =Def. b continuant_part_of c at t & b and c are not identical. (axiom label in BFO2 Reference: [004-001]) properContinuantPartOfAt b proper_continuant_part_of c at t =Def. b continuant_part_of c at t & b and c are not identical. (axiom label in BFO2 Reference: [004-001]) (iff (properContinuantPartOfAt a b t) (and (continuantPartOfAt a b t) (not (= a b)))) // axiom label in BFO2 CLIF: [004-001] part of continuant at some time (forall (x y t) (if (and (continuantPartOfAt x y t) (IndependentContinuant x)) (locatedInAt x y t))) // axiom label in BFO2 CLIF: [047-002] [copied from inverse property 'has continuant part at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has continuant part at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has continuant part@en'(x,y,t) BFO2 Reference: continuantThe range for ‘t’ (as in all cases throughout this document unless otherwise specified) is: temporal region. [copied from inverse property 'has continuant part at some time'] b has_continuant_part c at t = Def. c continuant_part_of b at t. (axiom label in BFO2 Reference: [006-001]) (forall (x y t) (if (and (continuantPartOfAt x y t) (not (= x y))) (exists (z) (and (continuantPartOfAt z y t) (not (exists (w) (and (continuantPartOfAt w x t) (continuantPartOfAt w z t)))))))) // axiom label in BFO2 CLIF: [121-001] (iff (ImmaterialEntity a) (and (IndependentContinuant a) (not (exists (b t) (and (MaterialEntity b) (continuantPartOfAt b a t)))))) // axiom label in BFO2 CLIF: [028-001] (forall (x t) (if (Continuant x) (continuantPartOfAt x x t))) // axiom label in BFO2 CLIF: [111-002] (forall (x y t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y x t)) (= x y))) // axiom label in BFO2 CLIF: [120-001] (forall (x y z t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y z t)) (continuantPartOfAt x z t))) // axiom label in BFO2 CLIF: [110-001] BFO 2 Reference: Immaterial entities are in some cases continuant parts of their material hosts. Thus the hold of a ship, for example, is a part of the ship; it may itself have parts, which may have names (used for example by ship stow planners, customs inspectors, and the like). Immaterial entities under both 1. and 2. can be of zero, one, two or three dimensions. We define:a(immaterial entity)[Definition: a is an immaterial entity = Def. a is an independent continuant that has no material entities as parts. (axiom label in BFO2 Reference: [028-001]) c-part-of_st BFO 2 Reference: a (continuant or occurrent) part of itself. We appreciate that this is counterintuitive for some users, since it implies for example that President Obama is a part of himself. However it brings benefits in simplifying the logical formalism, and it captures an important feature of identity, namely that it is the limit case of mereological inclusion. BFO2 Reference: continuant (forall (x y t) (if (exists (v) (and (continuantPartOfAt v x t) (continuantPartOfAt v y t))) (exists (z) (forall (u w) (iff (iff (continuantPartOfAt w u t) (and (continuantPartOfAt w x t) (continuantPartOfAt w y t))) (= z u)))))) // axiom label in BFO2 CLIF: [122-001] Mary’s arm continuant_part_of Mary in the time of her life prior to her operation continuantPartOfAt Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'part of continuant at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'part of continuant@en'(x,y,t) b continuant_part_of c at t =Def. b is a part of c at t & t is a time & b and c are continuants. (axiom label in BFO2 Reference: [002-001]) continuant_part_of is antisymmetric. (axiom label in BFO2 Reference: [120-001]) continuant_part_of is reflexive (every continuant entity is a continuant_part_of itself). (axiom label in BFO2 Reference: [111-002]) continuant_part_of is transitive. (axiom label in BFO2 Reference: [110-001]) continuant_part_of satisfies unique product. (axiom label in BFO2 Reference: [122-001]) continuant_part_of satisfies weak supplementation. (axiom label in BFO2 Reference: [121-001]) if b continuant_part_of c at t and b is an independent continuant, then b is located_in c at t. (axiom label in BFO2 Reference: [047-002]) the Northern hemisphere of the planet Earth is a part of the planet Earth at all times at which the planet Earth exists. BFO 2 Reference: Immaterial entities are in some cases continuant parts of their material hosts. Thus the hold of a ship, for example, is a part of the ship; it may itself have parts, which may have names (used for example by ship stow planners, customs inspectors, and the like). Immaterial entities under both 1. and 2. can be of zero, one, two or three dimensions. We define:a(immaterial entity)[Definition: a is an immaterial entity = Def. a is an independent continuant that has no material entities as parts. (axiom label in BFO2 Reference: [028-001]) continuant_part_of is reflexive (every continuant entity is a continuant_part_of itself). (axiom label in BFO2 Reference: [111-002]) (forall (x y t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y x t)) (= x y))) // axiom label in BFO2 CLIF: [120-001] continuant_part_of is antisymmetric. (axiom label in BFO2 Reference: [120-001]) continuant_part_of satisfies unique product. (axiom label in BFO2 Reference: [122-001]) continuant_part_of satisfies weak supplementation. (axiom label in BFO2 Reference: [121-001]) (forall (x y t) (if (and (continuantPartOfAt x y t) (IndependentContinuant x)) (locatedInAt x y t))) // axiom label in BFO2 CLIF: [047-002] (forall (x y z t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y z t)) (continuantPartOfAt x z t))) // axiom label in BFO2 CLIF: [110-001] (iff (ImmaterialEntity a) (and (IndependentContinuant a) (not (exists (b t) (and (MaterialEntity b) (continuantPartOfAt b a t)))))) // axiom label in BFO2 CLIF: [028-001] (forall (x t) (if (Continuant x) (continuantPartOfAt x x t))) // axiom label in BFO2 CLIF: [111-002] continuant_part_of is transitive. (axiom label in BFO2 Reference: [110-001]) (forall (x y t) (if (exists (v) (and (continuantPartOfAt v x t) (continuantPartOfAt v y t))) (exists (z) (forall (u w) (iff (iff (continuantPartOfAt w u t) (and (continuantPartOfAt w x t) (continuantPartOfAt w y t))) (= z u)))))) // axiom label in BFO2 CLIF: [122-001] if b continuant_part_of c at t and b is an independent continuant, then b is located_in c at t. (axiom label in BFO2 Reference: [047-002]) (forall (x y t) (if (and (continuantPartOfAt x y t) (not (= x y))) (exists (z) (and (continuantPartOfAt z y t) (not (exists (w) (and (continuantPartOfAt w x t) (continuantPartOfAt w z t)))))))) // axiom label in BFO2 CLIF: [121-001] b continuant_part_of c at t =Def. b is a part of c at t & t is a time & b and c are continuants. (axiom label in BFO2 Reference: [002-001]) part of continuant at all times (forall (x y t) (if (exists (v) (and (continuantPartOfAt v x t) (continuantPartOfAt v y t))) (exists (z) (forall (u w) (iff (iff (continuantPartOfAt w u t) (and (continuantPartOfAt w x t) (continuantPartOfAt w y t))) (= z u)))))) // axiom label in BFO2 CLIF: [122-001] BFO2 Reference: continuant (forall (x y t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y x t)) (= x y))) // axiom label in BFO2 CLIF: [120-001] continuantPartOfAt (forall (x y z t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y z t)) (continuantPartOfAt x z t))) // axiom label in BFO2 CLIF: [110-001] [copied from inverse property 'has continuant part at all times that part exists'] forall(t) exists_at(y,t) -> exists_at(x,t) and 'has continuant part'(x,y,t) c-part-of_at BFO2 Reference: continuantThe range for ‘t’ (as in all cases throughout this document unless otherwise specified) is: temporal region. (forall (x y t) (if (and (continuantPartOfAt x y t) (IndependentContinuant x)) (locatedInAt x y t))) // axiom label in BFO2 CLIF: [047-002] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'part of continuant at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'part of continuant@en(x,y,t)'. (forall (x y t) (if (and (continuantPartOfAt x y t) (not (= x y))) (exists (z) (and (continuantPartOfAt z y t) (not (exists (w) (and (continuantPartOfAt w x t) (continuantPartOfAt w z t)))))))) // axiom label in BFO2 CLIF: [121-001] (forall (x t) (if (Continuant x) (continuantPartOfAt x x t))) // axiom label in BFO2 CLIF: [111-002] (iff (ImmaterialEntity a) (and (IndependentContinuant a) (not (exists (b t) (and (MaterialEntity b) (continuantPartOfAt b a t)))))) // axiom label in BFO2 CLIF: [028-001] BFO 2 Reference: Immaterial entities are in some cases continuant parts of their material hosts. Thus the hold of a ship, for example, is a part of the ship; it may itself have parts, which may have names (used for example by ship stow planners, customs inspectors, and the like). Immaterial entities under both 1. and 2. can be of zero, one, two or three dimensions. We define:a(immaterial entity)[Definition: a is an immaterial entity = Def. a is an independent continuant that has no material entities as parts. (axiom label in BFO2 Reference: [028-001]) BFO 2 Reference: a (continuant or occurrent) part of itself. We appreciate that this is counterintuitive for some users, since it implies for example that President Obama is a part of himself. However it brings benefits in simplifying the logical formalism, and it captures an important feature of identity, namely that it is the limit case of mereological inclusion. Mary’s arm continuant_part_of Mary in the time of her life prior to her operation [copied from inverse property 'has continuant part at all times that part exists'] This is a binary version of a ternary time-indexed, instance level, relation. Unlike the rest of the temporalized relations which temporally quantify over existence of the subject of the relation, this relation temporally quantifies over the existence of the object of the relation. The relation is provided tentatively, to assess whether the GO needs such a relation. It is inverse of 'part of continuant at all times' b continuant_part_of c at t =Def. b is a part of c at t & t is a time & b and c are continuants. (axiom label in BFO2 Reference: [002-001]) continuant_part_of is antisymmetric. (axiom label in BFO2 Reference: [120-001]) continuant_part_of is reflexive (every continuant entity is a continuant_part_of itself). (axiom label in BFO2 Reference: [111-002]) continuant_part_of is transitive. (axiom label in BFO2 Reference: [110-001]) continuant_part_of satisfies unique product. (axiom label in BFO2 Reference: [122-001]) continuant_part_of satisfies weak supplementation. (axiom label in BFO2 Reference: [121-001]) if b continuant_part_of c at t and b is an independent continuant, then b is located_in c at t. (axiom label in BFO2 Reference: [047-002]) the Northern hemisphere of the planet Earth is a part of the planet Earth at all times at which the planet Earth exists. continuant_part_of is transitive. (axiom label in BFO2 Reference: [110-001]) (iff (ImmaterialEntity a) (and (IndependentContinuant a) (not (exists (b t) (and (MaterialEntity b) (continuantPartOfAt b a t)))))) // axiom label in BFO2 CLIF: [028-001] continuant_part_of satisfies weak supplementation. (axiom label in BFO2 Reference: [121-001]) (forall (x y t) (if (and (continuantPartOfAt x y t) (IndependentContinuant x)) (locatedInAt x y t))) // axiom label in BFO2 CLIF: [047-002] (forall (x y t) (if (and (continuantPartOfAt x y t) (not (= x y))) (exists (z) (and (continuantPartOfAt z y t) (not (exists (w) (and (continuantPartOfAt w x t) (continuantPartOfAt w z t)))))))) // axiom label in BFO2 CLIF: [121-001] BFO 2 Reference: Immaterial entities are in some cases continuant parts of their material hosts. Thus the hold of a ship, for example, is a part of the ship; it may itself have parts, which may have names (used for example by ship stow planners, customs inspectors, and the like). Immaterial entities under both 1. and 2. can be of zero, one, two or three dimensions. We define:a(immaterial entity)[Definition: a is an immaterial entity = Def. a is an independent continuant that has no material entities as parts. (axiom label in BFO2 Reference: [028-001]) if b continuant_part_of c at t and b is an independent continuant, then b is located_in c at t. (axiom label in BFO2 Reference: [047-002]) (forall (x y t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y x t)) (= x y))) // axiom label in BFO2 CLIF: [120-001] b continuant_part_of c at t =Def. b is a part of c at t & t is a time & b and c are continuants. (axiom label in BFO2 Reference: [002-001]) (forall (x t) (if (Continuant x) (continuantPartOfAt x x t))) // axiom label in BFO2 CLIF: [111-002] (forall (x y z t) (if (and (continuantPartOfAt x y t) (continuantPartOfAt y z t)) (continuantPartOfAt x z t))) // axiom label in BFO2 CLIF: [110-001] continuant_part_of satisfies unique product. (axiom label in BFO2 Reference: [122-001]) continuant_part_of is reflexive (every continuant entity is a continuant_part_of itself). (axiom label in BFO2 Reference: [111-002]) continuant_part_of is antisymmetric. (axiom label in BFO2 Reference: [120-001]) (forall (x y t) (if (exists (v) (and (continuantPartOfAt v x t) (continuantPartOfAt v y t))) (exists (z) (forall (u w) (iff (iff (continuantPartOfAt w u t) (and (continuantPartOfAt w x t) (continuantPartOfAt w y t))) (= z u)))))) // axiom label in BFO2 CLIF: [122-001] has continuant part at some time [copied from inverse property 'part of continuant at some time'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'part of continuant at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'part of continuant@en'(x,y,t) [copied from inverse property 'part of continuant at some time'] b continuant_part_of c at t =Def. b is a part of c at t & t is a time & b and c are continuants. (axiom label in BFO2 Reference: [002-001]) [copied from inverse property 'part of continuant at some time'] Mary’s arm continuant_part_of Mary in the time of her life prior to her operation (iff (hasContinuantPartAt a b t) (continuantPartOfAt b a t)) // axiom label in BFO2 CLIF: [006-001] c-has-part_st Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance level, relation. The BFO reading of the binary relation 'has continuant part at some time@en' is: exists t, exists_at(x,t) & exists_at(y,t) & 'has continuant part@en'(x,y,t) [copied from inverse property 'part of continuant at some time'] BFO2 Reference: continuant [copied from inverse property 'part of continuant at some time'] BFO 2 Reference: a (continuant or occurrent) part of itself. We appreciate that this is counterintuitive for some users, since it implies for example that President Obama is a part of himself. However it brings benefits in simplifying the logical formalism, and it captures an important feature of identity, namely that it is the limit case of mereological inclusion. [copied from inverse property 'part of continuant at some time'] BFO2 Reference: continuantThe range for ‘t’ (as in all cases throughout this document unless otherwise specified) is: temporal region. hasContinuantPartAt [copied from inverse property 'part of continuant at some time'] the Northern hemisphere of the planet Earth is a part of the planet Earth at all times at which the planet Earth exists. [copied from inverse property 'part of continuant at some time'] BFO 2 Reference: Immaterial entities are in some cases continuant parts of their material hosts. Thus the hold of a ship, for example, is a part of the ship; it may itself have parts, which may have names (used for example by ship stow planners, customs inspectors, and the like). Immaterial entities under both 1. and 2. can be of zero, one, two or three dimensions. We define:a(immaterial entity)[Definition: a is an immaterial entity = Def. a is an independent continuant that has no material entities as parts. (axiom label in BFO2 Reference: [028-001]) b has_continuant_part c at t = Def. c continuant_part_of b at t. (axiom label in BFO2 Reference: [006-001]) b has_continuant_part c at t = Def. c continuant_part_of b at t. (axiom label in BFO2 Reference: [006-001]) (iff (hasContinuantPartAt a b t) (continuantPartOfAt b a t)) // axiom label in BFO2 CLIF: [006-001] has proper temporal part has-t-ppart history of [copied from inverse property 'has history'] b has_history c iff c history_of b [XXX-001 b history_of c if c is a material entity or site and b is a history that is the unique history of cAxiom: if b history_of c and b history_of d then c=d [XXX-001 historyOf history-of has history hasHistory [copied from inverse property 'history of'] b history_of c if c is a material entity or site and b is a history that is the unique history of cAxiom: if b history_of c and b history_of d then c=d [XXX-001 b has_history c iff c history_of b [XXX-001 has-history part of continuant at all times that whole exists [copied from inverse property 'has continuant part at all times'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'has continuant part at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'has continuant part@en(x,y,t)'. This is a binary version of a ternary time-indexed, instance level, relation. Unlike the rest of the temporalized relations which temporally quantify over existence of the subject of the relation, this relation temporally quantifies over the existence of the object of the relation. The relation is provided tentatively, to assess whether the GO needs such a relation. It is inverse of 'has continuant part at all times' forall(t) exists_at(y,t) -> exists_at(x,t) and 'part of continuant'(x,y,t) [copied from inverse property 'has continuant part at all times'] b has_continuant_part c at t = Def. c continuant_part_of b at t. (axiom label in BFO2 Reference: [006-001]) c-part-of-object_at This is a binary version of a ternary time-indexed, instance level, relation. Unlike the rest of the temporalized relations which temporally quantify over existence of the subject of the relation, this relation temporally quantifies over the existence of the object of the relation. The relation is provided tentatively, to assess whether the GO needs such a relation. It is inverse of 'has continuant part at all times' forall(t) exists_at(y,t) -> exists_at(x,t) and 'part of continuant'(x,y,t) has continuant part at all times that part exists [copied from inverse property 'part of continuant at all times'] BFO2 Reference: continuant [copied from inverse property 'part of continuant at all times'] the Northern hemisphere of the planet Earth is a part of the planet Earth at all times at which the planet Earth exists. c-has-part-object_at forall(t) exists_at(y,t) -> exists_at(x,t) and 'has continuant part'(x,y,t) [copied from inverse property 'part of continuant at all times'] b continuant_part_of c at t =Def. b is a part of c at t & t is a time & b and c are continuants. (axiom label in BFO2 Reference: [002-001]) [copied from inverse property 'part of continuant at all times'] Mary’s arm continuant_part_of Mary in the time of her life prior to her operation This is a binary version of a ternary time-indexed, instance level, relation. Unlike the rest of the temporalized relations which temporally quantify over existence of the subject of the relation, this relation temporally quantifies over the existence of the object of the relation. The relation is provided tentatively, to assess whether the GO needs such a relation. It is inverse of 'part of continuant at all times' [copied from inverse property 'part of continuant at all times'] BFO 2 Reference: Immaterial entities are in some cases continuant parts of their material hosts. Thus the hold of a ship, for example, is a part of the ship; it may itself have parts, which may have names (used for example by ship stow planners, customs inspectors, and the like). Immaterial entities under both 1. and 2. can be of zero, one, two or three dimensions. We define:a(immaterial entity)[Definition: a is an immaterial entity = Def. a is an independent continuant that has no material entities as parts. (axiom label in BFO2 Reference: [028-001]) [copied from inverse property 'part of continuant at all times'] BFO2 Reference: continuantThe range for ‘t’ (as in all cases throughout this document unless otherwise specified) is: temporal region. [copied from inverse property 'part of continuant at all times'] Alan Ruttenberg: This is a binary version of a ternary time-indexed, instance-level, relation. The BFO reading of the binary relation 'part of continuant at all times@en' is: forall(t) exists_at(x,t) -> exists_at(y,t) and 'part of continuant@en(x,y,t)'. [copied from inverse property 'part of continuant at all times'] BFO 2 Reference: a (continuant or occurrent) part of itself. We appreciate that this is counterintuitive for some users, since it implies for example that President Obama is a part of himself. However it brings benefits in simplifying the logical formalism, and it captures an important feature of identity, namely that it is the limit case of mereological inclusion. forall(t) exists_at(y,t) -> exists_at(x,t) and 'has continuant part'(x,y,t) This is a binary version of a ternary time-indexed, instance level, relation. Unlike the rest of the temporalized relations which temporally quantify over existence of the subject of the relation, this relation temporally quantifies over the existence of the object of the relation. The relation is provided tentatively, to assess whether the GO needs such a relation. It is inverse of 'part of continuant at all times' is about Smith, Ceusters, Ruttenberg, 2000 years of philosophy This document is about information artifacts and their representations is_about is a (currently) primitive relation that relates an information artifact to an entity. person:Alan Ruttenberg denotes A person's name denotes the person. A variable name in a computer program denotes some piece of memory. Lexically equivalent strings can denote different things, for instance "Alan" can denote different people. In each case of use, there is a case of the denotation relation obtaining, between "Alan" and the person that is being named. Conversations with Barry Smith, Werner Ceusters, Bjoern Peters, Michel Dumontier, Melanie Courtot, James Malone, Bill Hogan denotes is a primitive, instance-level, relation obtaining between an information content entity and some portion of reality. Denotation is what happens when someone creates an information content entity E in order to specifically refer to something. The only relation between E and the thing is that E can be used to 'pick out' the thing. This relation connects those two together. Freedictionary.com sense 3: To signify directly; refer to specifically person:Alan Ruttenberg imported from imported from For external terms/classes, the ontology from which the term was imported GROUP:OBI:<http://purl.obolibrary.org/obo/obi> PERSON:Alan Ruttenberg PERSON:Melanie Courtot imported from results_in capable_of has_material_basis_in is_denoted_by initially participates in Yu Asiyah Lin, Yongqun He a 'participate in' relation that indicates the participant initiates the process, and the process will not start without the existence of the participant. attenuated disposition realized in A short cut relation or a property chain that link a Brucella mutant(mo) with a host-pathogen interaction proccess(p) mo 'has disposition at some time' 'attenuated disposition' ∩ 'attenuated disposition' 'realized in' p encoded_by encodes has_temporal_interval has_scattered_temporal_region lacks_part It was used in this ontology as: B.abortus S19 vaccine, lacks C terminal part of EryC protien, so B. abortus S19 lacks_part Brucella EryC protein The generation of this relation was inspired by W. Ceusters et al in 'Negative findings in electronic health records and biomedical ontologies: a realist approach' published in Int J Med Inform,76 Suppl 3, S326-33, 2007/03/21. After talking to W. Ceusters and getting help from other experts, the definition of this relation is updated and follows the instruction provided in the paper: Hoehndorf R, Oellrich A, Dumontier M, Kelso J, Rebholz-Schuhmann D, Herre H. Relations as patterns: bridging the gap between OBO and OWL. BMC Bioinformatics. 2010 Aug 31;11:441. doi: 10.1186/1471-2105-11-441. PMID: 20807438. YL, YH Hoehndorf R, Oellrich A, Dumontier M, Kelso J, Rebholz-Schuhmann D, Herre H. Relations as patterns: bridging the gap between OBO and OWL. BMC Bioinformatics. 2010 Aug 31;11:441. doi: 10.1186/1471-2105-11-441. PMID: 20807438. The object property lacks_part represents a relation between instances of two classes; specifically, the meaning of X lacks-part Y is that all instances of X have no instance of Y as part: ?X subClassOf: not has-part some ?Y. agent_in_compromised_process agent_in_compromised_process_comparing_to_wild_type This term is used for linking the mutant and its compromised process, such as reduced intracellular replication, when compared to wild type. It is a short relation of mutant has_weakened_disposition_of_process some 'disposition of undergoing process' and ('realized in' some process) YL, YH has_specified_input A relation between a planned process and a continuant participating in that process that is not created during the process. The presence of the continuant during the process is explicitly specified in the plan specification which the process realizes the concretization of. has_specified_input is_specified_input_of A relation between a planned process and a continuant participating in that process that is not created during the process. The presence of the continuant during the process is explicitly specified in the plan specification which the process realizes the concretization of. is_specified_input_of has_specified_output A relation between a planned process and a continuant participating in that process. The presence of the continuant at the end of the process is explicitly specified in the objective specification which the process realizes the concretization of. has_specified_output obsolete_has_function Relation between an independent continuant and a function. obsolete_has_function is_specified_output_of A relation between a planned process and a continuant participating in that process. The presence of the continuant at the end of the process is explicitly specified in the objective specification which the process realizes the concretization of. is_specified_output_of obsolete_has_role A relation between a continuant C and a role R. The reciprocal relation of role_of. obsolete_has_role achieves_planned_objective This relation obtains between a planned process and a objective specification when the criteria specified in the objective specification are met at the end of the planned process. achieves_planned_objective is genome of organism a 'part of continuant at some time' relation that incides a genome belongs to a organism. Yongqun He, Bin Zhao is gene of organism Oliver He, Yue Liu a relation between a gene and the organism where this gene belongs to the organism in nature. It does not include a foreign gene that is transferred to an organism by a genetic engineering method. inheres in A dependent inheres in its bearer at all times for which the dependent exists. a relation between a specifically dependent continuant (the dependent) and an independent continuant (the bearer), in which the dependent specifically depends on the bearer for its existence inheres in inheres_in this fragility inheres in this vase this red color inheres in this apple bearer_of Examples: red eye bearer_of redness relationship OBO_REL:0000027 has_inherer A relation between an entity and a dependent continuant; the reciprocal relation of inheres_in GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm has_inherent participates in a relation between a continuant and a process, in which the continuant is somehow involved in the process participates in participates_in this blood clot participates in this blood coagulation this input material (or this output material) participates in this process this investigator participates in this investigation has participant Has_participant is a primitive instance-level relation between a process, a continuant, and a time at which the continuant participates in some way in the process. The relation obtains, for example, when this particular process of oxygen exchange across this particular alveolar membrane has_participant this particular sample of hemoglobin at this particular time. a relation between a process and a continuant, in which the continuant is somehow involved in the process has participant http://www.obofoundry.org/ro/#OBO_REL:has_participant has_participant this blood coagulation has participant this blood clot this investigation has participant this investigator this process has participant this input material (or this output material) starts_during X starts_during Y iff: (start(Y) before_or_simultaneous_with start(X)) AND (start(X) before_or_simultaneous_with end(Y)) io happens_during X happens_during Y iff: (start(Y) before_or_simultaneous_with start(X)) AND (end(X) before_or_simultaneous_with end(Y)) d during ends_during o overlaps X ends_during Y iff: ((start(Y) before_or_simultaneous_with end(X)) AND end(X) before_or_simultaneous_with end(Y). develops_from regulates x regulates y if and only if the x is the realization of a function to exert an effect on the frequency, rate or extent of y David Hill Tanya Berardini Chris Mungall GO negatively regulates x negatively regulates y if and only if the progression of x reduces the frequency, rate or extent of y positively regulates x positively regulates y if and only if the progression of x increases the frequency, rate or extent of y capable_of actively participates in agent in x actively participates in y if and only if x participates in y and x realizes some active role has active participant 'heart development' has active participant some Shh protein has agent This may be obsoleted and replaced by the original 'has agent' relation x has participant y if and only if x realizes some active role that inheres in y temporally related to https://docs.google.com/document/d/1kBv1ep_9g3sTR-SD3jqzFqhuwo9TPNF-l-9fUDbO6rM/edit?pli=1 Allen Do not use this relation directly. It is ended as a grouping for relations between occurrents involving the relative timing of their starts and ends. A relation that holds between two occurrents. This is a grouping relation that collects together all the Allen relations. ends with finished by x ends with y if and only if x has part y and the time point at which x ends is equivalent to the time point at which y ends. Formally: α(y) > α(x) ∧ ω(y) = ω(x), where α is a function that maps a process to a start point, and ω is a function that maps a process to an end point. has output p has output c if either: p has direct output c or p has output input c. See subrelations for definitions. produces results in formation of results_in_formation_of has product an annotation of gene X to anatomical structure formation with results_in_formation_of UBERON:0000007 (pituitary gland) means that at the beginning of the process a pituitary gland does not exist and at the end of the process a pituitary gland exists. GOC:mtg_berkeley_2013 The relationship linking a cell and its participation in a process that results in the transition of a cell such that is can only develop into a single cell type when left in its environment. every "endocardial cushion formation" (GO:0003272) results_in_formation_of some "endocardial cushion" (UBERON:0002062) transformation of x transformation of y if x is the immediate transformation of y, or is linked to y through a chain of transformation relationships has_disposition relationship has_function heart has_function to-pump-blood OBO_REL:0000031 relationship Relation between an independent continuant and a function. GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm has_output Examples: secretory cells. Should this be has_function (export of ...) relationship C has_output C' GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm has_role relationship OBO_REL:0000033 A relation between a continuant C and a role R. The reciprocal relation of role_of. GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm inheres_in This relation links qualities, functions, dispositions and other dependent continuants to their bearers. Examples: A particular shape that inheres in a lung; The redness that ineres in a Drosophila eye; Catalytic activity function inheres_in catalytic molecule. Note that inherence is a functional relation: if x inheres_in y at t and x inheres_in z at t, then y=z. We leave open the possibility of a relation multiply_inheres_in, such as between a gene sequence and the multiple chromosomes it multiply inheres in. The super-relation of both inheres_in and multiply_inheres_in would be depends_on relationship OBO_REL:0000026 has_bearer A relation between a dependent continuant D and an entity E. D inheres_in E iff: given any d that instantiates D at t, there exists some e that instantiates E at t and d *inheres_in* e at t. Here *inheres_in* is the primitive instance level relation. GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm negatively_regulates relationship A regulation relation in which the unfolding of the regulating process *decreases* the frequency, rate or extent of the regulated process positively_regulates relationship A regulation relation in which the unfolding of the regulating process *increases* the frequency, rate or extent of the regulated process realized_by NOTE: there appears to be some consistency in usage as to whether processes or continuants realize OBO_REL:0000035 relationship OBO_REL:realized_as executed_during has_realization executed_during Relation between a realizable and a process. Reciprocal relation of realizes GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm Relation between a realizable and a process. Reciprocal relation of realizes GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm has_realization realizes The process of 'histidine catabolism' (GO:0006548) realizes the function 'histidine ammonia lyase activity' (GO:0004397) (note: here 'activity' denotes a function and not a process). We leave open the possibility of defining in future the sub-relations directly_realizes (as bewteen a function and it's functioning) and indirectly_realizes. NOTE: there appears to be some consistency in usage as to whether processes or continuants realize OBO_REL:0000034 relationship involves_execution_of Relation between a process and a function, where the unfolding of the process requires the execution of the function. Class level: P realizes F iff: given any p that instantiates P, there exists some f, t such that f instantiates F at t and p *realizes* f. Here, *realizes* is the primitive instance level relation GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm is_realization_of has_function_part executes regulates relationship A relation between a process and a process or quality. A regulates B if the unfolding of A affects the frequency, rate or extent of B. A is called the regulating process, B the regulates process results_in_formation_of Example: autophagic vacuole formation results_in_formation_of autophagic vacuole. macromolecular complex assembly results_in_formation_of a macromolecule. Note: essentially the same as biosynthesis, although in biosynthesis the assembly is via chemical reactions relationship P results_in_formation_of C : any instance of P gives rise to a C from the parts of C. Formally: forall pP, exists some c such that c instantiates C at end-of p, and c has some parts c1, c2, ... such that the parts are connected at the end-of p and disconected at the start-of p GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm results_in_creation_of results_in_assembly_of unfolds_in Example: oocyte axis determination : The establishment, maintenance and elaboration of an axis in the oocyte. This process unfolds_in the oocyte relationship P unfolds_in C : the execution of P is spatially contained by C. forall pP, forall c' partipates_in p, c' located_in C at t, for some t in P GOC:cjm http://purl.obolibrary.org/obo/GOC_cjm lacks_plasma_membrane_part only_in_taxon has_part relationship OBO_REL:0000003 part_of Parthood as a relation between instances: The primitive instance-level relation p part_of p1 is illustrated in assertions such as: this instance of rhodopsin mediated phototransduction part_of this instance of visual perception. This relation satisfies at least the following standard axioms of mereology: reflexivity (for all p, p part_of p); anti-symmetry (for all p, p1, if p part_of p1 and p1 part_of p then p and p1 are identical); and transitivity (for all p, p1, p2, if p part_of p1 and p1 part_of p2, then p part_of p2). Analogous axioms hold also for parthood as a relation between spatial regions. For parthood as a relation between continuants, these axioms need to be modified to take account of the incorporation of a temporal argument. Thus for example the axiom of transitivity for continuants will assert that if c part_of c1 at t and c1 part_of c2 at t, then also c part_of c2 at t. Parthood as a relation between classes: To define part_of as a relation between classes we again need to distinguish the two cases of continuants and processes, even though the explicit reference to instants of time now falls away. For continuants, we have C part_of C1 if and only if any instance of C at any time is an instance-level part of some instance of C1 at that time, as for example in: cell nucleus part_ of cell. OBO_REL:0000002 There is controversy about this relation intended to represent the relation between some arbitrary physical thing that is used as a represention/proxy/pointer to something else relationship For continuants: C part_of C' if and only if: given any c that instantiates C at a time t, there is some c' such that c' instantiates C' at time t, and c *part_of* c' at t. For processes: P part_of P' if and only if: given any p that instantiates P at a time t, there is some p' such that p' instantiates P' at time t, and p *part_of* p' at t. (Here *part_of* is the instance-level part-relation.) PMID:15892874 http://purl.org/obo/owl/PMID#PMID_15892874 hasDurationinDays what type we should use? for 6 weeks, 2 weeks, 3 weeks... and so forth has_gene_symbol entity entity Entity An entity is anything that exists or has existed or will exist. (axiom label in BFO2 Reference: [001-001]) BFO 2 Reference: In all areas of empirical inquiry we encounter general terms of two sorts. First are general terms which refer to universals or types:animaltuberculosissurgical procedurediseaseSecond, are general terms used to refer to groups of entities which instantiate a given universal but do not correspond to the extension of any subuniversal of that universal because there is nothing intrinsic to the entities in question by virtue of which they – and only they – are counted as belonging to the given group. Examples are: animal purchased by the Emperortuberculosis diagnosed on a Wednesdaysurgical procedure performed on a patient from Stockholmperson identified as candidate for clinical trial #2056-555person who is signatory of Form 656-PPVpainting by Leonardo da VinciSuch terms, which represent what are called ‘specializations’ in [81 Entity doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example Werner Ceusters 'portions of reality' include 4 sorts, entities (as BFO construes them), universals, configurations, and relations. It is an open question as to whether entities as construed in BFO will at some point also include these other portions of reality. See, for example, 'How to track absolutely everything' at http://www.referent-tracking.com/_RTU/papers/CeustersICbookRevised.pdf Julius Caesar Verdi’s Requiem entity the Second World War your body mass index Entity doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example Werner Ceusters 'portions of reality' include 4 sorts, entities (as BFO construes them), universals, configurations, and relations. It is an open question as to whether entities as construed in BFO will at some point also include these other portions of reality. See, for example, 'How to track absolutely everything' at http://www.referent-tracking.com/_RTU/papers/CeustersICbookRevised.pdf per discussion with Barry Smith An entity is anything that exists or has existed or will exist. (axiom label in BFO2 Reference: [001-001]) continuant continuant Continuant (forall (x) (if (Continuant x) (Entity x))) // axiom label in BFO2 CLIF: [008-002] (forall (x y) (if (and (Continuant x) (exists (t) (continuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [009-002] (forall (x y) (if (and (Continuant x) (exists (t) (hasContinuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [126-001] (forall (x) (if (Material Entity x) (exists (t) (and (TemporalRegion t) (existsAt x t))))) // axiom label in BFO2 CLIF: [011-002] A continuant is an entity that persists, endures, or continues to exist through time while maintaining its identity. (axiom label in BFO2 Reference: [008-002]) An entity that exists in full at any time in which it exists at all, persists through time while maintaining its identity and has no temporal parts. An entity that exists in full at any time in which it exists at all, persists through time while maintaining its identity and has no temporal parts. BFO 2 Reference: Continuant entities are entities which can be sliced to yield parts only along the spatial dimension, yielding for example the parts of your table which we call its legs, its top, its nails. ‘My desk stretches from the window to the door. It has spatial parts, and can be sliced (in space) in two. With respect to time, however, a thing is a continuant.’ [60, p. 240 Continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example, in an expansion involving bringing in some of Ceuster's other portions of reality, questions are raised as to whether universals are continuants if b is a continuant and if, for some t, c has_continuant_part b at t, then c is a continuant. (axiom label in BFO2 Reference: [126-001]) if b is a continuant and if, for some t, cis continuant_part of b at t, then c is a continuant. (axiom label in BFO2 Reference: [009-002]) if b is a material entity, then there is some temporal interval (referred to below as a one-dimensional temporal region) during which b exists. (axiom label in BFO2 Reference: [011-002]) (forall (x y) (if (and (Continuant x) (exists (t) (continuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [009-002] if b is a continuant and if, for some t, cis continuant_part of b at t, then c is a continuant. (axiom label in BFO2 Reference: [009-002]) (forall (x) (if (Material Entity x) (exists (t) (and (TemporalRegion t) (existsAt x t))))) // axiom label in BFO2 CLIF: [011-002] Continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example, in an expansion involving bringing in some of Ceuster's other portions of reality, questions are raised as to whether universals are continuants if b is a continuant and if, for some t, c has_continuant_part b at t, then c is a continuant. (axiom label in BFO2 Reference: [126-001]) if b is a material entity, then there is some temporal interval (referred to below as a one-dimensional temporal region) during which b exists. (axiom label in BFO2 Reference: [011-002]) (forall (x) (if (Continuant x) (Entity x))) // axiom label in BFO2 CLIF: [008-002] A continuant is an entity that persists, endures, or continues to exist through time while maintaining its identity. (axiom label in BFO2 Reference: [008-002]) (forall (x y) (if (and (Continuant x) (exists (t) (hasContinuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [126-001] occurrent (forall (x) (iff (Occurrent x) (and (Entity x) (exists (y) (temporalPartOf y x))))) // axiom label in BFO2 CLIF: [079-001] An entity that has temporal parts and that happens, unfolds or develops through time. BFO 2 Reference: every occurrent that is not a temporal or spatiotemporal region is s-dependent on some independent continuant that is not a spatial region Simons uses different terminology for relations of occurrents to regions: Denote the spatio-temporal location of a given occurrent e by 'spn[e]' and call this region its span. We may say an occurrent is at its span, in any larger region, and covers any smaller region. Now suppose we have fixed a frame of reference so that we can speak not merely of spatio-temporal but also of spatial regions (places) and temporal regions (times). The spread of an occurrent, (relative to a frame of reference) is the space it exactly occupies, and its spell is likewise the time it exactly occupies. We write 'spr[e]' and `spl[e]' respectively for the spread and spell of e, omitting mention of the frame. (forall (x) (if (Occurrent x) (exists (r) (and (SpatioTemporalRegion r) (occupiesSpatioTemporalRegion x r))))) // axiom label in BFO2 CLIF: [108-001] An occurrent is an entity that unfolds itself in time or it is the instantaneous boundary of such an entity (for example a beginning or an ending) or it is a temporal or spatiotemporal region which such an entity occupies_temporal_region or occupies_spatiotemporal_region. (axiom label in BFO2 Reference: [077-002]) BFO 2 Reference: s-dependence obtains between every process and its participants in the sense that, as a matter of necessity, this process could not have existed unless these or those participants existed also. A process may have a succession of participants at different phases of its unfolding. Thus there may be different players on the field at different times during the course of a football game; but the process which is the entire game s-depends_on all of these players nonetheless. Some temporal parts of this process will s-depend_on on only some of the players. Occurrent Occurrent doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. An example would be the sum of a process and the process boundary of another process. occurrent Every occurrent occupies_spatiotemporal_region some spatiotemporal region. (axiom label in BFO2 Reference: [108-001]) b is an occurrent entity iff b is an entity that has temporal parts. (axiom label in BFO2 Reference: [079-001]) Simons uses different terminology for relations of occurrents to regions: Denote the spatio-temporal location of a given occurrent e by 'spn[e]' and call this region its span. We may say an occurrent is at its span, in any larger region, and covers any smaller region. Now suppose we have fixed a frame of reference so that we can speak not merely of spatio-temporal but also of spatial regions (places) and temporal regions (times). The spread of an occurrent, (relative to a frame of reference) is the space it exactly occupies, and its spell is likewise the time it exactly occupies. We write 'spr[e]' and `spl[e]' respectively for the spread and spell of e, omitting mention of the frame. b is an occurrent entity iff b is an entity that has temporal parts. (axiom label in BFO2 Reference: [079-001]) Every occurrent occupies_spatiotemporal_region some spatiotemporal region. (axiom label in BFO2 Reference: [108-001]) per discussion with Barry Smith Occurrent doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. An example would be the sum of a process and the process boundary of another process. An occurrent is an entity that unfolds itself in time or it is the instantaneous boundary of such an entity (for example a beginning or an ending) or it is a temporal or spatiotemporal region which such an entity occupies_temporal_region or occupies_spatiotemporal_region. (axiom label in BFO2 Reference: [077-002]) (forall (x) (iff (Occurrent x) (and (Entity x) (exists (y) (temporalPartOf y x))))) // axiom label in BFO2 CLIF: [079-001] (forall (x) (if (Occurrent x) (exists (r) (and (SpatioTemporalRegion r) (occupiesSpatioTemporalRegion x r))))) // axiom label in BFO2 CLIF: [108-001] independent continuant IndependentContinuant (forall (x t) (if (and (IndependentContinuant x) (existsAt x t)) (exists (y) (and (Entity y) (specificallyDependsOnAt y x t))))) // axiom label in BFO2 CLIF: [018-002] (iff (IndependentContinuant a) (and (Continuant a) (not (exists (b t) (specificallyDependsOnAt a b t))))) // axiom label in BFO2 CLIF: [017-002] (forall (x t) (if (IndependentContinuant x) (exists (r) (and (SpatialRegion r) (locatedInAt x r t))))) // axiom label in BFO2 CLIF: [134-001] A continuant that is a bearer of quality and realizable entity entities, in which other entities inhere and which itself cannot inhere in anything. For any independent continuant b and any time t there is some spatial region r such that b is located_in r at t. (axiom label in BFO2 Reference: [134-001]) For every independent continuant b and time t during the region of time spanned by its life, there are entities which s-depends_on b during t. (axiom label in BFO2 Reference: [018-002]) a heart a molecule a spatial region an atom an organism ic a chair a leg an orchestra. b is an independent continuant = Def. b is a continuant which is such that there is no c and no t such that b s-depends_on c at t. (axiom label in BFO2 Reference: [017-002]) substantial entity the bottom right portion of a human torso the interior of your mouth (forall (x t) (if (and (IndependentContinuant x) (existsAt x t)) (exists (y) (and (Entity y) (specificallyDependsOnAt y x t))))) // axiom label in BFO2 CLIF: [018-002] For every independent continuant b and time t during the region of time spanned by its life, there are entities which s-depends_on b during t. (axiom label in BFO2 Reference: [018-002]) (forall (x t) (if (IndependentContinuant x) (exists (r) (and (SpatialRegion r) (locatedInAt x r t))))) // axiom label in BFO2 CLIF: [134-001] b is an independent continuant = Def. b is a continuant which is such that there is no c and no t such that b s-depends_on c at t. (axiom label in BFO2 Reference: [017-002]) For any independent continuant b and any time t there is some spatial region r such that b is located_in r at t. (axiom label in BFO2 Reference: [134-001]) (iff (IndependentContinuant a) (and (Continuant a) (not (exists (b t) (specificallyDependsOnAt a b t))))) // axiom label in BFO2 CLIF: [017-002] spatial region true true (forall (x) (if (SpatialRegion x) (Continuant x))) // axiom label in BFO2 CLIF: [035-001] s-region SpatialRegion (forall (x y t) (if (and (SpatialRegion x) (continuantPartOfAt y x t)) (SpatialRegion y))) // axiom label in BFO2 CLIF: [036-001] A spatial region is a continuant entity that is a continuant_part_of spaceR as defined relative to some frame R. (axiom label in BFO2 Reference: [035-001]) All continuant parts of spatial regions are spatial regions. (axiom label in BFO2 Reference: [036-001]) BFO 2 Reference: Spatial regions do not participate in processes. Spatial region doesn't have a closure axiom because the subclasses don't exhaust all possibilites. An example would be the union of a spatial point and a spatial line that doesn't overlap the point, or two spatial lines that intersect at a single point. In both cases the resultant spatial region is neither 0-dimensional, 1-dimensional, 2-dimensional, or 3-dimensional. true (forall (x y t) (if (and (SpatialRegion x) (continuantPartOfAt y x t)) (SpatialRegion y))) // axiom label in BFO2 CLIF: [036-001] per discussion with Barry Smith Spatial region doesn't have a closure axiom because the subclasses don't exhaust all possibilites. An example would be the union of a spatial point and a spatial line that doesn't overlap the point, or two spatial lines that intersect at a single point. In both cases the resultant spatial region is neither 0-dimensional, 1-dimensional, 2-dimensional, or 3-dimensional. (forall (x) (if (SpatialRegion x) (Continuant x))) // axiom label in BFO2 CLIF: [035-001] All continuant parts of spatial regions are spatial regions. (axiom label in BFO2 Reference: [036-001]) true A spatial region is a continuant entity that is a continuant_part_of spaceR as defined relative to some frame R. (axiom label in BFO2 Reference: [035-001]) temporal region true true (forall (x) (if (TemporalRegion x) (Occurrent x))) // axiom label in BFO2 CLIF: [100-001] Every temporal region t is such that t occupies_temporal_region t. (axiom label in BFO2 Reference: [119-002]) Temporal region doesn't have a closure axiom because the subclasses don't exhaust all possibilites. An example would be the mereological sum of a temporal instant and a temporal interval that doesn't overlap the instant. In this case the resultant temporal region is neither 0-dimensional nor 1-dimensional TemporalRegion t-region (forall (r) (if (TemporalRegion r) (occupiesTemporalRegion r r))) // axiom label in BFO2 CLIF: [119-002] (forall (x y) (if (and (TemporalRegion x) (occurrentPartOf y x)) (TemporalRegion y))) // axiom label in BFO2 CLIF: [101-001] A temporal region is an occurrent entity that is part of time as defined relative to some reference frame. (axiom label in BFO2 Reference: [100-001]) All parts of temporal regions are temporal regions. (axiom label in BFO2 Reference: [101-001]) Every temporal region t is such that t occupies_temporal_region t. (axiom label in BFO2 Reference: [119-002]) per discussion with Barry Smith Temporal region doesn't have a closure axiom because the subclasses don't exhaust all possibilites. An example would be the mereological sum of a temporal instant and a temporal interval that doesn't overlap the instant. In this case the resultant temporal region is neither 0-dimensional nor 1-dimensional (forall (r) (if (TemporalRegion r) (occupiesTemporalRegion r r))) // axiom label in BFO2 CLIF: [119-002] (forall (x y) (if (and (TemporalRegion x) (occurrentPartOf y x)) (TemporalRegion y))) // axiom label in BFO2 CLIF: [101-001] (forall (x) (if (TemporalRegion x) (Occurrent x))) // axiom label in BFO2 CLIF: [100-001] All parts of temporal regions are temporal regions. (axiom label in BFO2 Reference: [101-001]) true A temporal region is an occurrent entity that is part of time as defined relative to some reference frame. (axiom label in BFO2 Reference: [100-001]) true two-dimensional spatial region 2d-s-region TwoDimensionalSpatialRegion (forall (x) (if (TwoDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [039-001] A two-dimensional spatial region is a spatial region that is of two dimensions. (axiom label in BFO2 Reference: [039-001]) an infinitely thin plane in space. the surface of a sphere-shaped part of space A two-dimensional spatial region is a spatial region that is of two dimensions. (axiom label in BFO2 Reference: [039-001]) (forall (x) (if (TwoDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [039-001] spatiotemporal region true true st-region (forall (x) (if (SpatioTemporalRegion x) (exists (y) (and (TemporalRegion y) (temporallyProjectsOnto x y))))) // axiom label in BFO2 CLIF: [098-001] (forall (x) (if (SpatioTemporalRegion x) (Occurrent x))) // axiom label in BFO2 CLIF: [095-001] (forall (x y) (if (and (SpatioTemporalRegion x) (occurrentPartOf y x)) (SpatioTemporalRegion y))) // axiom label in BFO2 CLIF: [096-001] (forall (r) (if (SpatioTemporalRegion r) (occupiesSpatioTemporalRegion r r))) // axiom label in BFO2 CLIF: [107-002] A spatiotemporal region is an occurrent entity that is part of spacetime. (axiom label in BFO2 Reference: [095-001]) Each spatiotemporal region at any time t projects_onto some spatial region at t. (axiom label in BFO2 Reference: [099-001]) SpatiotemporalRegion (forall (x t) (if (SpatioTemporalRegion x) (exists (y) (and (SpatialRegion y) (spatiallyProjectsOntoAt x y t))))) // axiom label in BFO2 CLIF: [099-001] All parts of spatiotemporal regions are spatiotemporal regions. (axiom label in BFO2 Reference: [096-001]) Each spatiotemporal region projects_onto some temporal region. (axiom label in BFO2 Reference: [098-001]) Every spatiotemporal region occupies_spatiotemporal_region itself. Every spatiotemporal region s is such that s occupies_spatiotemporal_region s. (axiom label in BFO2 Reference: [107-002]) the spatiotemporal region occupied by a human life the spatiotemporal region occupied by a process of cellular meiosis. the spatiotemporal region occupied by the development of a cancer tumor (forall (x t) (if (SpatioTemporalRegion x) (exists (y) (and (SpatialRegion y) (spatiallyProjectsOntoAt x y t))))) // axiom label in BFO2 CLIF: [099-001] Each spatiotemporal region projects_onto some temporal region. (axiom label in BFO2 Reference: [098-001]) true (forall (x y) (if (and (SpatioTemporalRegion x) (occurrentPartOf y x)) (SpatioTemporalRegion y))) // axiom label in BFO2 CLIF: [096-001] All parts of spatiotemporal regions are spatiotemporal regions. (axiom label in BFO2 Reference: [096-001]) Every spatiotemporal region s is such that s occupies_spatiotemporal_region s. (axiom label in BFO2 Reference: [107-002]) (forall (r) (if (SpatioTemporalRegion r) (occupiesSpatioTemporalRegion r r))) // axiom label in BFO2 CLIF: [107-002] (forall (x) (if (SpatioTemporalRegion x) (Occurrent x))) // axiom label in BFO2 CLIF: [095-001] A spatiotemporal region is an occurrent entity that is part of spacetime. (axiom label in BFO2 Reference: [095-001]) (forall (x) (if (SpatioTemporalRegion x) (exists (y) (and (TemporalRegion y) (temporallyProjectsOnto x y))))) // axiom label in BFO2 CLIF: [098-001] Each spatiotemporal region at any time t projects_onto some spatial region at t. (axiom label in BFO2 Reference: [099-001]) true process Process (iff (Process a) (and (Occurrent a) (exists (b) (properTemporalPartOf b a)) (exists (c t) (and (MaterialEntity c) (specificallyDependsOnAt a c t))))) // axiom label in BFO2 CLIF: [083-003] An occurrent that has temporal proper parts and for some time t, p s-depends_on some material entity at t. BFO 2 Reference: The realm of occurrents is less pervasively marked by the presence of natural units than is the case in the realm of independent continuants. Thus there is here no counterpart of ‘object’. In BFO 1.0 ‘process’ served as such a counterpart. In BFO 2.0 ‘process’ is, rather, the occurrent counterpart of ‘material entity’. Those natural – as contrasted with engineered, which here means: deliberately executed – units which do exist in the realm of occurrents are typically either parasitic on the existence of natural units on the continuant side, or they are fiat in nature. Thus we can count lives; we can count football games; we can count chemical reactions performed in experiments or in chemical manufacturing. We cannot count the processes taking place, for instance, in an episode of insect mating behavior.Even where natural units are identifiable, for example cycles in a cyclical process such as the beating of a heart or an organism’s sleep/wake cycle, the processes in question form a sequence with no discontinuities (temporal gaps) of the sort that we find for instance where billiard balls or zebrafish or planets are separated by clear spatial gaps. Lives of organisms are process units, but they too unfold in a continuous series from other, prior processes such as fertilization, and they unfold in turn in continuous series of post-life processes such as post-mortem decay. Clear examples of boundaries of processes are almost always of the fiat sort (midnight, a time of death as declared in an operating theater or on a death certificate, the initiation of a state of war) a process of cell-division, \ a beating of the heart a process of meiosis a process of sleeping p is a process = Def. p is an occurrent that has temporal proper parts and for some time t, p s-depends_on some material entity at t. (axiom label in BFO2 Reference: [083-003]) process the course of a disease the flight of a bird the life of an organism your process of aging. (iff (Process a) (and (Occurrent a) (exists (b) (properTemporalPartOf b a)) (exists (c t) (and (MaterialEntity c) (specificallyDependsOnAt a c t))))) // axiom label in BFO2 CLIF: [083-003] p is a process = Def. p is an occurrent that has temporal proper parts and for some time t, p s-depends_on some material entity at t. (axiom label in BFO2 Reference: [083-003]) disposition (forall (x) (if (Disposition x) (and (RealizableEntity x) (exists (y) (and (MaterialEntity y) (bearerOfAt x y t)))))) // axiom label in BFO2 CLIF: [062-002] Disposition (forall (x t) (if (and (RealizableEntity x) (existsAt x t)) (exists (y) (and (MaterialEntity y) (specificallyDepends x y t))))) // axiom label in BFO2 CLIF: [063-002] BFO 2 Reference: Dispositions exist along a strength continuum. Weaker forms of disposition are realized in only a fraction of triggering cases. These forms occur in a significant number of cases of a similar type [89 BFO 2 Reference: Dispositions exist along a strength continuum. Weaker forms of disposition are realized in only a fraction of triggering cases. These forms occur in a significant number of cases of a similar type. disposition If b is a realizable entity then for all t at which b exists, b s-depends_on some material entity at t. (axiom label in BFO2 Reference: [063-002]) an atom of element X has the disposition to decay to an atom of element Y b is a disposition means: b is a realizable entity & b’s bearer is some material entity & b is such that if it ceases to exist, then its bearer is physically changed, & b’s realization occurs when and because this bearer is in some special physical circumstances, & this realization occurs in virtue of the bearer’s physical make-up. (axiom label in BFO2 Reference: [062-002]) certain people have a predisposition to colon cancer children are innately disposed to categorize objects in certain ways. the cell wall is disposed to filter chemicals in endocitosis and exocitosis the cell wall is disposed to filter chemicals in endocytosis and exocytosis (forall (x t) (if (and (RealizableEntity x) (existsAt x t)) (exists (y) (and (MaterialEntity y) (specificallyDepends x y t))))) // axiom label in BFO2 CLIF: [063-002] b is a disposition means: b is a realizable entity & b’s bearer is some material entity & b is such that if it ceases to exist, then its bearer is physically changed, & b’s realization occurs when and because this bearer is in some special physical circumstances, & this realization occurs in virtue of the bearer’s physical make-up. (axiom label in BFO2 Reference: [062-002]) (forall (x) (if (Disposition x) (and (RealizableEntity x) (exists (y) (and (MaterialEntity y) (bearerOfAt x y t)))))) // axiom label in BFO2 CLIF: [062-002] If b is a realizable entity then for all t at which b exists, b s-depends_on some material entity at t. (axiom label in BFO2 Reference: [063-002]) realizable entity (forall (x) (if (RealizableEntity x) (and (SpecificallyDependentContinuant x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (inheresIn x y)))))) // axiom label in BFO2 CLIF: [058-002] (forall (x t) (if (RealizableEntity x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (bearerOfAt y x t))))) // axiom label in BFO2 CLIF: [060-002] A specifically dependent continuant that inheres in continuant entities and are not exhibited in full at every time in which it inheres in an entity or group of entities. The exhibition or actualization of a realizable entity is a particular manifestation, functioning or process that occurs under certain circumstances. All realizable dependent continuants have independent continuants that are not spatial regions as their bearers. (axiom label in BFO2 Reference: [060-002]) RealizableEntity To say that b is a realizable entity is to say that b is a specifically dependent continuant that inheres in some independent continuant which is not a spatial region and is of a type instances of which are realized in processes of a correlated type. (axiom label in BFO2 Reference: [058-002]) realizable the disposition of this piece of metal to conduct electricity. the disposition of your blood to coagulate the function of your reproductive organs the role of being a doctor the role of this boundary to delineate where Utah and Colorado meet To say that b is a realizable entity is to say that b is a specifically dependent continuant that inheres in some independent continuant which is not a spatial region and is of a type instances of which are realized in processes of a correlated type. (axiom label in BFO2 Reference: [058-002]) All realizable dependent continuants have independent continuants that are not spatial regions as their bearers. (axiom label in BFO2 Reference: [060-002]) (forall (x) (if (RealizableEntity x) (and (SpecificallyDependentContinuant x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (inheresIn x y)))))) // axiom label in BFO2 CLIF: [058-002] (forall (x t) (if (RealizableEntity x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (bearerOfAt y x t))))) // axiom label in BFO2 CLIF: [060-002] zero-dimensional spatial region 0d-s-region ZeroDimensionalSpatialRegion (forall (x) (if (ZeroDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [037-001] A zero-dimensional spatial region is a point in space. (axiom label in BFO2 Reference: [037-001]) A zero-dimensional spatial region is a point in space. (axiom label in BFO2 Reference: [037-001]) (forall (x) (if (ZeroDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [037-001] quality (forall (x) (if (Quality x) (SpecificallyDependentContinuant x))) // axiom label in BFO2 CLIF: [055-001] quality Quality (forall (x) (if (exists (t) (and (existsAt x t) (Quality x))) (forall (t_1) (if (existsAt x t_1) (Quality x))))) // axiom label in BFO2 CLIF: [105-001] If an entity is a quality at any time that it exists, then it is a quality at every time that it exists. (axiom label in BFO2 Reference: [105-001]) a quality is a specifically dependent continuant that, in contrast to roles and dispositions, does not require any further process in order to be realized. (axiom label in BFO2 Reference: [055-001]) the ambient temperature of this portion of air the color of a tomato the length of the circumference of your waist the mass of this piece of gold. the shape of your nose the shape of your nostril a quality is a specifically dependent continuant that, in contrast to roles and dispositions, does not require any further process in order to be realized. (axiom label in BFO2 Reference: [055-001]) (forall (x) (if (exists (t) (and (existsAt x t) (Quality x))) (forall (t_1) (if (existsAt x t_1) (Quality x))))) // axiom label in BFO2 CLIF: [105-001] (forall (x) (if (Quality x) (SpecificallyDependentContinuant x))) // axiom label in BFO2 CLIF: [055-001] If an entity is a quality at any time that it exists, then it is a quality at every time that it exists. (axiom label in BFO2 Reference: [105-001]) specifically dependent continuant (iff (SpecificallyDependentContinuant a) (and (Continuant a) (forall (t) (if (existsAt a t) (exists (b) (and (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))))))) // axiom label in BFO2 CLIF: [050-003] (iff (RelationalSpecificallyDependentContinuant a) (and (SpecificallyDependentContinuant a) (forall (t) (exists (b c) (and (not (SpatialRegion b)) (not (SpatialRegion c)) (not (= b c)) (not (exists (d) (and (continuantPartOfAt d b t) (continuantPartOfAt d c t)))) (specificallyDependsOnAt a b t) (specificallyDependsOnAt a c t)))))) // axiom label in BFO2 CLIF: [131-004] SpecificallyDependentContinuant A continuant that inheres in or is borne by other entities. Every instance of A requires some specific instance of B which must always be the same. Reciprocal specifically dependent continuants: the function of this key to open this lock and the mutually dependent disposition of this lock: to be opened by this key Specifically dependent continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. We're not sure what else will develop here, but for example there are questions such as what are promises, obligation, etc. b is a relational specifically dependent continuant = Def. b is a specifically dependent continuant and there are n &gt; 1 independent continuants c1, … cn which are not spatial regions are such that for all 1 i &lt; j n, ci and cj share no common parts, are such that for each 1 i n, b s-depends_on ci at every time t during the course of b’s existence (axiom label in BFO2 Reference: [131-004]) b is a specifically dependent continuant = Def. b is a continuant & there is some independent continuant c which is not a spatial region and which is such that b s-depends_on c at every time t during the course of b’s existence. (axiom label in BFO2 Reference: [050-003]) of one-sided specifically dependent continuants: the mass of this tomato of relational dependent continuants (multiple bearers): John’s love for Mary, the ownership relation between John and this statue, the relation of authority between John and his subordinates. sdc the disposition of this fish to decay the function of this heart: to pump blood the mutual dependence of proton donors and acceptors in chemical reactions [79 the mutual dependence of the role predator and the role prey as played by two organisms in a given interaction the pink color of a medium rare piece of grilled filet mignon at its center the role of being a doctor the shape of this hole. the smell of this portion of mozzarella b is a relational specifically dependent continuant = Def. b is a specifically dependent continuant and there are n &gt; 1 independent continuants c1, … cn which are not spatial regions are such that for all 1 i &lt; j n, ci and cj share no common parts, are such that for each 1 i n, b s-depends_on ci at every time t during the course of b’s existence (axiom label in BFO2 Reference: [131-004]) (iff (SpecificallyDependentContinuant a) (and (Continuant a) (forall (t) (if (existsAt a t) (exists (b) (and (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))))))) // axiom label in BFO2 CLIF: [050-003] (iff (RelationalSpecificallyDependentContinuant a) (and (SpecificallyDependentContinuant a) (forall (t) (exists (b c) (and (not (SpatialRegion b)) (not (SpatialRegion c)) (not (= b c)) (not (exists (d) (and (continuantPartOfAt d b t) (continuantPartOfAt d c t)))) (specificallyDependsOnAt a b t) (specificallyDependsOnAt a c t)))))) // axiom label in BFO2 CLIF: [131-004] b is a specifically dependent continuant = Def. b is a continuant & there is some independent continuant c which is not a spatial region and which is such that b s-depends_on c at every time t during the course of b’s existence. (axiom label in BFO2 Reference: [050-003]) per discussion with Barry Smith Specifically dependent continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. We're not sure what else will develop here, but for example there are questions such as what are promises, obligation, etc. role Role role (forall (x) (if (Role x) (RealizableEntity x))) // axiom label in BFO2 CLIF: [061-001] BFO 2 Reference: One major family of examples of non-rigid universals involves roles, and ontologies developed for corresponding administrative purposes may consist entirely of representatives of entities of this sort. Thus ‘professor’, defined as follows,b instance_of professor at t =Def. there is some c, c instance_of professor role & c inheres_in b at t.denotes a non-rigid universal and so also do ‘nurse’, ‘student’, ‘colonel’, ‘taxpayer’, and so forth. (These terms are all, in the jargon of philosophy, phase sortals.) By using role terms in definitions, we can create a BFO conformant treatment of such entities drawing on the fact that, while an instance of professor may be simultaneously an instance of trade union member, no instance of the type professor role is also (at any time) an instance of the type trade union member role (any more than any instance of the type color is at any time an instance of the type length).If an ontology of employment positions should be defined in terms of roles following the above pattern, this enables the ontology to do justice to the fact that individuals instantiate the corresponding universals – professor, sergeant, nurse – only during certain phases in their lives. John’s role of husband to Mary is dependent on Mary’s role of wife to John, and both are dependent on the object aggregate comprising John and Mary as member parts joined together through the relational quality of being married. b is a role means: b is a realizable entity & b exists because there is some single bearer that is in some special physical, social, or institutional set of circumstances in which this bearer does not have to be& b is not such that, if it ceases to exist, then the physical make-up of the bearer is thereby changed. (axiom label in BFO2 Reference: [061-001]) the priest role the role of a boundary to demarcate two neighboring administrative territories the role of a building in serving as a military target the role of a stone in marking a property boundary the role of subject in a clinical trial the student role b is a role means: b is a realizable entity & b exists because there is some single bearer that is in some special physical, social, or institutional set of circumstances in which this bearer does not have to be& b is not such that, if it ceases to exist, then the physical make-up of the bearer is thereby changed. (axiom label in BFO2 Reference: [061-001]) (forall (x) (if (Role x) (RealizableEntity x))) // axiom label in BFO2 CLIF: [061-001] fiat object BFO 2 Reference: Most examples of fiat object parts are associated with theoretically drawn divisions fiat-object FiatObjectPart (forall (x) (if (FiatObjectPart x) (and (MaterialEntity x) (forall (t) (if (existsAt x t) (exists (y) (and (Object y) (properContinuantPartOfAt x y t)))))))) // axiom label in BFO2 CLIF: [027-004] b is a fiat object part = Def. b is a material entity which is such that for all times t, if b exists at t then there is some object c such that b proper continuant_part of c at t and c is demarcated from the remainder of c by a two-dimensional continuant fiat boundary. (axiom label in BFO2 Reference: [027-004]) or with divisions drawn by cognitive subjects for practical reasons, such as the division of a cake (before slicing) into (what will become) slices (and thus member parts of an object aggregate). However, this does not mean that fiat object parts are dependent for their existence on divisions or delineations effected by cognitive subjects. If, for example, it is correct to conceive geological layers of the Earth as fiat object parts of the Earth, then even though these layers were first delineated in recent times, still existed long before such delineation and what holds of these layers (for example that the oldest layers are also the lowest layers) did not begin to hold because of our acts of delineation.Treatment of material entity in BFOExamples viewed by some as problematic cases for the trichotomy of fiat object part, object, and object aggregate include: a mussel on (and attached to) a rock, a slime mold, a pizza, a cloud, a galaxy, a railway train with engine and multiple carriages, a clonal stand of quaking aspen, a bacterial community (biofilm), a broken femur. Note that, as Aristotle already clearly recognized, such problematic cases – which lie at or near the penumbra of instances defined by the categories in question – need not invalidate these categories. The existence of grey objects does not prove that there are not objects which are black and objects which are white; the existence of mules does not prove that there are not objects which are donkeys and objects which are horses. It does, however, show that the examples in question need to be addressed carefully in order to show how they can be fitted into the proposed scheme, for example by recognizing additional subdivisions [29 the FMA:regional parts of an intact human body. the Western hemisphere of the Earth the division of the brain into regions the division of the planet into hemispheres the dorsal and ventral surfaces of the body the upper and lower lobes of the left lung (forall (x) (if (FiatObjectPart x) (and (MaterialEntity x) (forall (t) (if (existsAt x t) (exists (y) (and (Object y) (properContinuantPartOfAt x y t)))))))) // axiom label in BFO2 CLIF: [027-004] b is a fiat object part = Def. b is a material entity which is such that for all times t, if b exists at t then there is some object c such that b proper continuant_part of c at t and c is demarcated from the remainder of c by a two-dimensional continuant fiat boundary. (axiom label in BFO2 Reference: [027-004]) one-dimensional spatial region (forall (x) (if (OneDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [038-001] OneDimensionalSpatialRegion 1d-s-region A one-dimensional spatial region is a line or aggregate of lines stretching from one point in space to another. (axiom label in BFO2 Reference: [038-001]) an edge of a cube-shaped portion of space. A one-dimensional spatial region is a line or aggregate of lines stretching from one point in space to another. (axiom label in BFO2 Reference: [038-001]) (forall (x) (if (OneDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [038-001] object aggregate ISBN:978-3-938793-98-5pp124-158#Thomas Bittner and Barry Smith, 'A Theory of Granular Partitions', in K. Munn and B. Smith (eds.), Applied Ontology: An Introduction, Frankfurt/Lancaster: ontos, 2008, 125-158. (forall (x) (if (ObjectAggregate x) (and (MaterialEntity x) (forall (t) (if (existsAt x t) (exists (y z) (and (Object y) (Object z) (memberPartOfAt y x t) (memberPartOfAt z x t) (not (= y z)))))) (not (exists (w t_1) (and (memberPartOfAt w x t_1) (not (Object w)))))))) // axiom label in BFO2 CLIF: [025-004] BFO 2 Reference: object aggregates may gain and lose parts while remaining numerically identical (one and the same individual) over time. This holds both for aggregates whose membership is determined naturally (the aggregate of cells in your body) and aggregates determined by fiat (a baseball team, a congressional committee). ObjectAggregate object-aggregate An entity a is an object aggregate if and only if there is a mutually exhaustive and pairwise disjoint partition of a into objects a collection of cells in a blood biobank. a swarm of bees is an aggregate of members who are linked together through natural bonds a symphony orchestra an organization is an aggregate whose member parts have roles of specific types (for example in a jazz band, a chess club, a football team) b is an object aggregate means: b is a material entity consisting exactly of a plurality of objects as member_parts at all times at which b exists. (axiom label in BFO2 Reference: [025-004]) defined by fiat: the aggregate of members of an organization defined through physical attachment: the aggregate of atoms in a lump of granite defined through physical containment: the aggregate of molecules of carbon dioxide in a sealed container defined via attributive delimitations such as: the patients in this hospital the aggregate of bearings in a constant velocity axle joint the aggregate of blood cells in your body the nitrogen atoms in the atmosphere the restaurants in Palo Alto your collection of Meissen ceramic plates. ISBN:978-3-938793-98-5pp124-158#Thomas Bittner and Barry Smith, 'A Theory of Granular Partitions', in K. Munn and B. Smith (eds.), Applied Ontology: An Introduction, Frankfurt/Lancaster: ontos, 2008, 125-158. (forall (x) (if (ObjectAggregate x) (and (MaterialEntity x) (forall (t) (if (existsAt x t) (exists (y z) (and (Object y) (Object z) (memberPartOfAt y x t) (memberPartOfAt z x t) (not (= y z)))))) (not (exists (w t_1) (and (memberPartOfAt w x t_1) (not (Object w)))))))) // axiom label in BFO2 CLIF: [025-004] b is an object aggregate means: b is a material entity consisting exactly of a plurality of objects as member_parts at all times at which b exists. (axiom label in BFO2 Reference: [025-004]) An entity a is an object aggregate if and only if there is a mutually exhaustive and pairwise disjoint partition of a into objects An entity a is an object aggregate if and only if there is a mutually exhaustive and pairwise disjoint partition of a into objects three-dimensional spatial region ThreeDimensionalSpatialRegion 3d-s-region (forall (x) (if (ThreeDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [040-001] A three-dimensional spatial region is a spatial region that is of three dimensions. (axiom label in BFO2 Reference: [040-001]) a cube-shaped region of space a sphere-shaped region of space, (forall (x) (if (ThreeDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [040-001] A three-dimensional spatial region is a spatial region that is of three dimensions. (axiom label in BFO2 Reference: [040-001]) site site Site (forall (x) (if (Site x) (ImmaterialEntity x))) // axiom label in BFO2 CLIF: [034-002] Manhattan Canyon) a hole in the interior of a portion of cheese a rabbit hole an air traffic control region defined in the airspace above an airport b is a site means: b is a three-dimensional immaterial entity that is (partially or wholly) bounded by a material entity or it is a three-dimensional immaterial part thereof. (axiom label in BFO2 Reference: [034-002]) the Grand Canyon the Piazza San Marco the cockpit of an aircraft the hold of a ship the interior of a kangaroo pouch the interior of the trunk of your car the interior of your bedroom the interior of your office the interior of your refrigerator the lumen of your gut your left nostril (a fiat part – the opening – of your left nasal cavity) b is a site means: b is a three-dimensional immaterial entity that is (partially or wholly) bounded by a material entity or it is a three-dimensional immaterial part thereof. (axiom label in BFO2 Reference: [034-002]) (forall (x) (if (Site x) (ImmaterialEntity x))) // axiom label in BFO2 CLIF: [034-002] object object Object BFO 2 Reference: BFO rests on the presupposition that at multiple micro-, meso- and macroscopic scales reality exhibits certain stable, spatially separated or separable material units, combined or combinable into aggregates of various sorts (for example organisms into what are called ‘populations’). Such units play a central role in almost all domains of natural science from particle physics to cosmology. Many scientific laws govern the units in question, employing general terms (such as ‘molecule’ or ‘planet’) referring to the types and subtypes of units, and also to the types and subtypes of the processes through which such units develop and interact. The division of reality into such natural units is at the heart of biological science, as also is the fact that these units may form higher-level units (as cells form multicellular organisms) and that they may also form aggregates of units, for example as cells form portions of tissue and organs form families, herds, breeds, species, and so on. At the same time, the division of certain portions of reality into engineered units (manufactured artifacts) is the basis of modern industrial technology, which rests on the distributed mass production of engineered parts through division of labor and on their assembly into larger, compound units such as cars and laptops. The division of portions of reality into units is one starting point for the phenomenon of counting. BFO 2 Reference: Each object is such that there are entities of which we can assert unproblematically that they lie in its interior, and other entities of which we can assert unproblematically that they lie in its exterior. This may not be so for entities lying at or near the boundary between the interior and exterior. This means that two objects – for example the two cells depicted in Figure 3 – may be such that there are material entities crossing their boundaries which belong determinately to neither cell. Something similar obtains in certain cases of conjoined twins (see below). BFO 2 Reference: To say that b is causally unified means: b is a material entity which is such that its material parts are tied together in such a way that, in environments typical for entities of the type in question,if c, a continuant part of b that is in the interior of b at t, is larger than a certain threshold size (which will be determined differently from case to case, depending on factors such as porosity of external cover) and is moved in space to be at t at a location on the exterior of the spatial region that had been occupied by b at t, then either b’s other parts will be moved in coordinated fashion or b will be damaged (be affected, for example, by breakage or tearing) in the interval between t and t.causal changes in one part of b can have consequences for other parts of b without the mediation of any entity that lies on the exterior of b. Material entities with no proper material parts would satisfy these conditions trivially. Candidate examples of types of causal unity for material entities of more complex sorts are as follows (this is not intended to be an exhaustive list):CU1: Causal unity via physical coveringHere the parts in the interior of the unified entity are combined together causally through a common membrane or other physical covering\. The latter points outwards toward and may serve a protective function in relation to what lies on the exterior of the entity [13, 47 BFO 2 Reference: an object is a maximal causally unified material entity BFO 2 Reference: ‘objects’ are sometimes referred to as ‘grains’ [74 atom b is an object means: b is a material entity which manifests causal unity of one or other of the types CUn listed above & is of a type (a material universal) instances of which are maximal relative to this criterion of causal unity. (axiom label in BFO2 Reference: [024-001]) cell cells and organisms engineered artifacts grain of sand molecule organelle organism planet solid portions of matter star b is an object means: b is a material entity which manifests causal unity of one or other of the types CUn listed above & is of a type (a material universal) instances of which are maximal relative to this criterion of causal unity. (axiom label in BFO2 Reference: [024-001]) generically dependent continuant gdc (iff (GenericallyDependentContinuant a) (and (Continuant a) (exists (b t) (genericallyDependsOnAt a b t)))) // axiom label in BFO2 CLIF: [074-001] GenericallyDependentContinuant The entries in your database are patterns instantiated as quality instances in your hard drive. The database itself is an aggregate of such patterns. When you create the database you create a particular instance of the generically dependent continuant type database. Each entry in the database is an instance of the generically dependent continuant type IAO: information content entity. b is a generically dependent continuant = Def. b is a continuant that g-depends_on one or more other entities. (axiom label in BFO2 Reference: [074-001]) the pdf file on your laptop, the pdf file that is a copy thereof on my laptop the sequence of this protein molecule; the sequence that is a copy thereof in that protein molecule. b is a generically dependent continuant = Def. b is a continuant that g-depends_on one or more other entities. (axiom label in BFO2 Reference: [074-001]) (iff (GenericallyDependentContinuant a) (and (Continuant a) (exists (b t) (genericallyDependsOnAt a b t)))) // axiom label in BFO2 CLIF: [074-001] function (forall (x) (if (Function x) (Disposition x))) // axiom label in BFO2 CLIF: [064-001] Function A function is a disposition that exists in virtue of the bearer’s physical make-up and this physical make-up is something the bearer possesses because it came into being, either through evolution (in the case of natural biological entities) or through intentional design (in the case of artifacts), in order to realize processes of a certain sort. (axiom label in BFO2 Reference: [064-001]) BFO 2 Reference: In the past, we have distinguished two varieties of function, artifactual function and biological function. These are not asserted subtypes of BFO:function however, since the same function – for example: to pump, to transport – can exist both in artifacts and in biological entities. The asserted subtypes of function that would be needed in order to yield a separate monoheirarchy are not artifactual function, biological function, etc., but rather transporting function, pumping function, etc. function the function of a hammer to drive in nails the function of a heart pacemaker to regulate the beating of a heart through electricity the function of amylase in saliva to break down starch into sugar (forall (x) (if (Function x) (Disposition x))) // axiom label in BFO2 CLIF: [064-001] A function is a disposition that exists in virtue of the bearer’s physical make-up and this physical make-up is something the bearer possesses because it came into being, either through evolution (in the case of natural biological entities) or through intentional design (in the case of artifacts), in order to realize processes of a certain sort. (axiom label in BFO2 Reference: [064-001]) process boundary (forall (x) (if (ProcessBoundary x) (exists (y) (and (ZeroDimensionalTemporalRegion y) (occupiesTemporalRegion x y))))) // axiom label in BFO2 CLIF: [085-002] (iff (ProcessBoundary a) (exists (p) (and (Process p) (temporalPartOf a p) (not (exists (b) (properTemporalPartOf b a)))))) // axiom label in BFO2 CLIF: [084-001] Every process boundary occupies_temporal_region a zero-dimensional temporal region. (axiom label in BFO2 Reference: [085-002]) p is a process boundary =Def. p is a temporal part of a process & p has no proper temporal parts. (axiom label in BFO2 Reference: [084-001]) p-boundary ProcessBoundary the boundary between the 2nd and 3rd year of your life. (forall (x) (if (ProcessBoundary x) (exists (y) (and (ZeroDimensionalTemporalRegion y) (occupiesTemporalRegion x y))))) // axiom label in BFO2 CLIF: [085-002] p is a process boundary =Def. p is a temporal part of a process & p has no proper temporal parts. (axiom label in BFO2 Reference: [084-001]) (iff (ProcessBoundary a) (exists (p) (and (Process p) (temporalPartOf a p) (not (exists (b) (properTemporalPartOf b a)))))) // axiom label in BFO2 CLIF: [084-001] Every process boundary occupies_temporal_region a zero-dimensional temporal region. (axiom label in BFO2 Reference: [085-002]) one-dimensional temporal region (forall (x) (if (OneDimensionalTemporalRegion x) (TemporalRegion x))) // axiom label in BFO2 CLIF: [103-001] OneDimensionalTemporalRegion 1d-t-region A one-dimensional temporal region is a temporal region that is extended. (axiom label in BFO2 Reference: [103-001]) BFO 2 Reference: A temporal interval is a special kind of one-dimensional temporal region, namely one that is self-connected (is without gaps or breaks). the temporal region during which a process occurs. (forall (x) (if (OneDimensionalTemporalRegion x) (TemporalRegion x))) // axiom label in BFO2 CLIF: [103-001] A one-dimensional temporal region is a temporal region that is extended. (axiom label in BFO2 Reference: [103-001]) material entity material (forall (x) (if (MaterialEntity x) (IndependentContinuant x))) // axiom label in BFO2 CLIF: [019-002] (forall (x) (if (and (Entity x) (exists (y t) (and (MaterialEntity y) (continuantPartOfAt y x t)))) (MaterialEntity x))) // axiom label in BFO2 CLIF: [020-002] (forall (x) (if (and (Entity x) (exists (y t) (and (MaterialEntity y) (continuantPartOfAt x y t)))) (MaterialEntity x))) // axiom label in BFO2 CLIF: [021-002] A material entity is an independent continuant that has some portion of matter as proper or improper continuant part. (axiom label in BFO2 Reference: [019-002]) An independent continuant that is spatially extended whose identity is independent of that of other entities and can be maintained through time. BFO 2 Reference: Material entities (continuants) can preserve their identity even while gaining and losing material parts. Continuants are contrasted with occurrents, which unfold themselves in successive temporal parts or phases [60 BFO 2 Reference: Object, Fiat Object Part and Object Aggregate are not intended to be exhaustive of Material Entity. Users are invited to propose new subcategories of Material Entity. BFO 2 Reference: ‘Matter’ is intended to encompass both mass and energy (we will address the ontological treatment of portions of energy in a later version of BFO). A portion of matter is anything that includes elementary particles among its proper or improper parts: quarks and leptons, including electrons, as the smallest particles thus far discovered; baryons (including protons and neutrons) at a higher level of granularity; atoms and molecules at still higher levels, forming the cells, organs, organisms and other material entities studied by biologists, the portions of rock studied by geologists, the fossils studied by paleontologists, and so on.Material entities are three-dimensional entities (entities extended in three spatial dimensions), as contrasted with the processes in which they participate, which are four-dimensional entities (entities extended also along the dimension of time).According to the FMA, material entities may have immaterial entities as parts – including the entities identified below as sites; for example the interior (or ‘lumen’) of your small intestine is a part of your body. BFO 2.0 embodies a decision to follow the FMA here. Every entity which has a material entity as continuant part is a material entity. (axiom label in BFO2 Reference: [020-002]) MaterialEntity a flame a forest fire a human being a hurricane a photon a puff of smoke a sea wave a tornado an aggregate of human beings. an energy wave an epidemic every entity of which a material entity is continuant part is also a material entity. (axiom label in BFO2 Reference: [021-002]) material entity the undetached arm of a human being (forall (x) (if (and (Entity x) (exists (y t) (and (MaterialEntity y) (continuantPartOfAt y x t)))) (MaterialEntity x))) // axiom label in BFO2 CLIF: [020-002] (forall (x) (if (and (Entity x) (exists (y t) (and (MaterialEntity y) (continuantPartOfAt x y t)))) (MaterialEntity x))) // axiom label in BFO2 CLIF: [021-002] (forall (x) (if (MaterialEntity x) (IndependentContinuant x))) // axiom label in BFO2 CLIF: [019-002] every entity of which a material entity is continuant part is also a material entity. (axiom label in BFO2 Reference: [021-002]) Every entity which has a material entity as continuant part is a material entity. (axiom label in BFO2 Reference: [020-002]) A material entity is an independent continuant that has some portion of matter as proper or improper continuant part. (axiom label in BFO2 Reference: [019-002]) continuant fiat boundary BFO 2 Reference: In BFO 1.1 the assumption was made that the external surface of a material entity such as a cell could be treated as if it were a boundary in the mathematical sense. The new document propounds the view that when we talk about external surfaces of material objects in this way then we are talking about something fiat. To be dealt with in a future version: fiat boundaries at different levels of granularity.More generally, the focus in discussion of boundaries in BFO 2.0 is now on fiat boundaries, which means: boundaries for which there is no assumption that they coincide with physical discontinuities. The ontology of boundaries becomes more closely allied with the ontology of regions. ContinuantFiatBoundary (iff (ContinuantFiatBoundary a) (and (ImmaterialEntity a) (exists (b) (and (or (ZeroDimensionalSpatialRegion b) (OneDimensionalSpatialRegion b) (TwoDimensionalSpatialRegion b)) (forall (t) (locatedInAt a b t)))) (not (exists (c t) (and (SpatialRegion c) (continuantPartOfAt c a t)))))) // axiom label in BFO2 CLIF: [029-001] BFO 2 Reference: a continuant fiat boundary is a boundary of some material entity (for example: the plane separating the Northern and Southern hemispheres; the North Pole), or it is a boundary of some immaterial entity (for example of some portion of airspace). Three basic kinds of continuant fiat boundary can be distinguished (together with various combination kinds [29 Every continuant fiat boundary is located at some spatial region at every time at which it exists b is a continuant fiat boundary = Def. b is an immaterial entity that is of zero, one or two dimensions and does not include a spatial region as part. (axiom label in BFO2 Reference: [029-001]) cf-boundary Continuant fiat boundary doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. An example would be the mereological sum of two-dimensional continuant fiat boundary and a one dimensional continuant fiat boundary that doesn't overlap it. The situation is analogous to temporal and spatial regions. Continuant fiat boundary doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. An example would be the mereological sum of two-dimensional continuant fiat boundary and a one dimensional continuant fiat boundary that doesn't overlap it. The situation is analogous to temporal and spatial regions. b is a continuant fiat boundary = Def. b is an immaterial entity that is of zero, one or two dimensions and does not include a spatial region as part. (axiom label in BFO2 Reference: [029-001]) (iff (ContinuantFiatBoundary a) (and (ImmaterialEntity a) (exists (b) (and (or (ZeroDimensionalSpatialRegion b) (OneDimensionalSpatialRegion b) (TwoDimensionalSpatialRegion b)) (forall (t) (locatedInAt a b t)))) (not (exists (c t) (and (SpatialRegion c) (continuantPartOfAt c a t)))))) // axiom label in BFO2 CLIF: [029-001] immaterial entity immaterial BFO 2 Reference: Immaterial entities are divided into two subgroups:boundaries and sites, which bound, or are demarcated in relation, to material entities, and which can thus change location, shape and size and as their material hosts move or change shape or size (for example: your nasal passage; the hold of a ship; the boundary of Wales (which moves with the rotation of the Earth) [38, 7, 10 ImmaterialEntity one-dimensional continuant fiat boundary OneDimensionalContinuantFiatBoundary (iff (OneDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (OneDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [032-001] 1d-cf-boundary The Equator a one-dimensional continuant fiat boundary is a continuous fiat line whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [032-001]) all geopolitical boundaries all lines of latitude and longitude the line separating the outer surface of the mucosa of the lower lip from the outer surface of the skin of the chin. the median sulcus of your tongue (iff (OneDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (OneDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [032-001] a one-dimensional continuant fiat boundary is a continuous fiat line whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [032-001]) process profile process-profile (forall (x y) (if (processProfileOf x y) (and (properContinuantPartOf x y) (exists (z t) (and (properOccurrentPartOf z y) (TemporalRegion t) (occupiesSpatioTemporalRegion x t) (occupiesSpatioTemporalRegion y t) (occupiesSpatioTemporalRegion z t) (not (exists (w) (and (occurrentPartOf w x) (occurrentPartOf w z))))))))) // axiom label in BFO2 CLIF: [094-005] (iff (ProcessProfile a) (exists (b) (and (Process b) (processProfileOf a b)))) // axiom label in BFO2 CLIF: [093-002] On a somewhat higher level of complexity are what we shall call rate process profiles, which are the targets of selective abstraction focused not on determinate quality magnitudes plotted over time, but rather on certain ratios between these magnitudes and elapsed times. A speed process profile, for example, is represented by a graph plotting against time the ratio of distance covered per unit of time. Since rates may change, and since such changes, too, may have rates of change, we have to deal here with a hierarchy of process profile universals at successive levels One important sub-family of rate process profiles is illustrated by the beat or frequency profiles of cyclical processes, illustrated by the 60 beats per minute beating process of John’s heart, or the 120 beats per minute drumming process involved in one of John’s performances in a rock band, and so on. Each such process includes what we shall call a beat process profile instance as part, a subtype of rate process profile in which the salient ratio is not distance covered but rather number of beat cycles per unit of time. Each beat process profile instance instantiates the determinable universal beat process profile. But it also instantiates multiple more specialized universals at lower levels of generality, selected from rate process profilebeat process profileregular beat process profile3 bpm beat process profile4 bpm beat process profileirregular beat process profileincreasing beat process profileand so on.In the case of a regular beat process profile, a rate can be assigned in the simplest possible fashion by dividing the number of cycles by the length of the temporal region occupied by the beating process profile as a whole. Irregular process profiles of this sort, for example as identified in the clinic, or in the readings on an aircraft instrument panel, are often of diagnostic significance. ProcessProfile The simplest type of process profiles are what we shall call ‘quality process profiles’, which are the process profiles which serve as the foci of the sort of selective abstraction that is involved when measurements are made of changes in single qualities, as illustrated, for example, by process profiles of mass, temperature, aortic pressure, and so on. b is a process_profile =Def. there is some process c such that b process_profile_of c (axiom label in BFO2 Reference: [093-002]) b process_profile_of c holds when b proper_occurrent_part_of c& there is some proper_occurrent_part d of c which has no parts in common with b & is mutually dependent on b& is such that b, c and d occupy the same temporal region (axiom label in BFO2 Reference: [094-005]) (forall (x y) (if (processProfileOf x y) (and (properContinuantPartOf x y) (exists (z t) (and (properOccurrentPartOf z y) (TemporalRegion t) (occupiesSpatioTemporalRegion x t) (occupiesSpatioTemporalRegion y t) (occupiesSpatioTemporalRegion z t) (not (exists (w) (and (occurrentPartOf w x) (occurrentPartOf w z))))))))) // axiom label in BFO2 CLIF: [094-005] b process_profile_of c holds when b proper_occurrent_part_of c& there is some proper_occurrent_part d of c which has no parts in common with b & is mutually dependent on b& is such that b, c and d occupy the same temporal region (axiom label in BFO2 Reference: [094-005]) b is a process_profile =Def. there is some process c such that b process_profile_of c (axiom label in BFO2 Reference: [093-002]) (iff (ProcessProfile a) (exists (b) (and (Process b) (processProfileOf a b)))) // axiom label in BFO2 CLIF: [093-002] relational quality 2 r-quality (iff (RelationalQuality a) (exists (b c t) (and (IndependentContinuant b) (IndependentContinuant c) (qualityOfAt a b t) (qualityOfAt a c t)))) // axiom label in BFO2 CLIF: [057-001] John’s role of husband to Mary is dependent on Mary’s role of wife to John, and both are dependent on the object aggregate comprising John and Mary as member parts joined together through the relational quality of being married. RelationalQuality a marriage bond, an instance of love, an obligation between one person and another. b is a relational quality = Def. for some independent continuants c, d and for some time t: b quality_of c at t & b quality_of d at t. (axiom label in BFO2 Reference: [057-001]) b is a relational quality = Def. for some independent continuants c, d and for some time t: b quality_of c at t & b quality_of d at t. (axiom label in BFO2 Reference: [057-001]) 2 (iff (RelationalQuality a) (exists (b c t) (and (IndependentContinuant b) (IndependentContinuant c) (qualityOfAt a b t) (qualityOfAt a c t)))) // axiom label in BFO2 CLIF: [057-001] two-dimensional continuant fiat boundary (iff (TwoDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (TwoDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [033-001] TwoDimensionalContinuantFiatBoundary 2d-cf-boundary a two-dimensional continuant fiat boundary (surface) is a self-connected fiat surface whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [033-001]) a two-dimensional continuant fiat boundary (surface) is a self-connected fiat surface whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [033-001]) (iff (TwoDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (TwoDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [033-001] zero-dimensional continuant fiat boundary (iff (ZeroDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (ZeroDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [031-001] 0d-cf-boundary ZeroDimensionalContinuantFiatBoundary a zero-dimensional continuant fiat boundary is a fiat point whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [031-001]) the geographic North Pole the point of origin of some spatial coordinate system. the quadripoint where the boundaries of Colorado, Utah, New Mexico, and Arizona meet zero dimension continuant fiat boundaries are not spatial points. Considering the example 'the quadripoint where the boundaries of Colorado, Utah, New Mexico, and Arizona meet' : There are many frames in which that point is zooming through many points in space. Whereas, no matter what the frame, the quadripoint is always in the same relation to the boundaries of Colorado, Utah, New Mexico, and Arizona. requested by Melanie Courtot zero dimension continuant fiat boundaries are not spatial points. Considering the example 'the quadripoint where the boundaries of Colorado, Utah, New Mexico, and Arizona meet' : There are many frames in which that point is zooming through many points in space. Whereas, no matter what the frame, the quadripoint is always in the same relation to the boundaries of Colorado, Utah, New Mexico, and Arizona. a zero-dimensional continuant fiat boundary is a fiat point whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [031-001]) (iff (ZeroDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (ZeroDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [031-001] zero-dimensional temporal region (forall (x) (if (ZeroDimensionalTemporalRegion x) (TemporalRegion x))) // axiom label in BFO2 CLIF: [102-001] ZeroDimensionalTemporalRegion 0d-t-region A zero-dimensional temporal region is a temporal region that is without extent. (axiom label in BFO2 Reference: [102-001]) a temporal region that is occupied by a process boundary right now temporal instant. the moment at which a child is born the moment at which a finger is detached in an industrial accident the moment of death. (forall (x) (if (ZeroDimensionalTemporalRegion x) (TemporalRegion x))) // axiom label in BFO2 CLIF: [102-001] A zero-dimensional temporal region is a temporal region that is without extent. (axiom label in BFO2 Reference: [102-001]) history history A history is a process that is the sum of the totality of processes taking place in the spatiotemporal region occupied by a material entity or site, including processes on the surface of the entity or within the cavities to which it serves as host. (axiom label in BFO2 Reference: [138-001]) History A history is a process that is the sum of the totality of processes taking place in the spatiotemporal region occupied by a material entity or site, including processes on the surface of the entity or within the cavities to which it serves as host. (axiom label in BFO2 Reference: [138-001]) anatomical entity Biological entity that is either an individual member of a biological species or constitutes the structural organization of an individual member of a biological species. anatomical entity glycerone phosphate A ketose phosphate that consists of glycerone bearing a single phospho substituent. DHAP cholesterol A cholestanoid consisting of cholestane having a double bond at the 5,6-position as well as a 3beta-hydroxy group. lipopolysaccharide Natural compounds consisting of a trisaccharide repeating unit (two heptose units and octulosonic acid) with oligosaccharide side chains and 3-hydroxytetradecanoic acid units (they are a major constituent of the cell walls of Gram-negative bacteria). bacterial lipopolysaccharide LPS deoxyribonucleic acid High molecular weight, linear polymers, composed of nucleotides containing deoxyribose and linked by phosphodiester bonds; DNA contain the genetic information of organisms. erythritol The meso-diastereomer of butane-1,2,3,4-tetrol. polysaccharide A biomacromolecule consisting of large numbers of monosaccharide residues linked glycosidically. This term is commonly used only for those containing more than ten monosaccharide residues. molecular entity molecular entity Any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer etc., identifiable as a separately distinguishable entity. Any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer etc., identifiable as a separately distinguishable entity. molecular entity glycosylphosphatidylinositol nucleic acid A macromolecule made up of nucleotide units and hydrolysable into certain pyrimidine or purine bases (usually adenine, cytosine, guanine, thymine, uracil), D-ribose or 2-deoxy-D-ribose and phosphoric acid. macromolecule A macromolecule is a molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass. polyatomic entity Any molecular entity consisting of more than one atom. nucleotide A nucleotide is a nucleoside phosphate. It is a phosphate ester that has a nucleoside moiety and has at least one phosphate moiety attached to the C-5 carbon of the ribose or deoxyribose moiety. double-stranded DNA GM1 ganglioside A sialotetraosylceramide consisting of a branched pentasaccharide made up from one sialyl residue, two galactose residues, one N-acetylgalactosamine residue and a glucose residue at the reducing end attached to N-stearoylsphingosine via a beta-linkage. O-polysaccharide A repetitive glycan polysaccharide contained within a lipopolysaccharide (LPS). The O-antigen is attached to the core oligosaccharide, and comprises the outermost domain of the LPS molecule. oligonucleotide A nucleobase-containing molecular entity with an oligomeric structure comprised of a linear sequence of nucleotide residues. An oligonucleotide must contain at least 2 nucleotide residues and typically contains fewer than 30. single-stranded DNA cell line cell Yongqun He, Matthew Brush, Sirarat Sarntivijai, Alexander Diehl, Jie Zheng, Yu Lin, Bjoern Peters A 'cell line cell' is a part of a cell line established through the passaging/selection of a primary cultured cells or the experimental modification of an existing cell line. New types of cell line cells are established after sufficient passaging of a primary culture to establish a stable and homogenous population that qualifies as a line (typically 1-20 passages), or following some spontaneous or experimental modification that confers novel characteristics to an existing line. A cell line cell typically has mutations of five or more genes compared to the original cell that derives the cell line cell. Some gene mutations may turn on some oncogenes. Cell line cells can be in active culture, stored in a quiescent state for future use (e.g. frozen in liquid nitrogen), or applied in experimental procedures. immortal cell line cell Yongqun He, Matthew Brush, Allen Xiang, Asiyah Yu Lin, Sirarat Sarntivijai, James Malone, Jie Zheng, Tomasz Adamusiak continuous cell line cell A cell line cell that is expected to be capable of an unlimited number of divisions, and is thus able to support indefinite propagation in vitro as part of an immortal cell line. permanent cell line cell immortal macrophage cell line cell ZX, YH a immortal phagocyte cell line that is derived from macrophage immortal epithelial cell line cell ZX, YH a immortal animal cell line that is derived from epithelial cell HeLa cell HyperCLDB: cl1601 ATCC: CCL-2 MeSH: D006367 HeLa J-774 HyperCLDB: cl2911 A murine macrophages cell line established from a tumor that arose in a female BALB/c mouse. Its growth is inhibited by dextran sulfate, purified protein derivative, and bacterial lipopolysaccharides. J774 cells have been used for numerous biochemical studies aimed at understanding the physiology of monocytes-macrophages. This cell line synthesizes large amounts of lysozyme and exhibits minor cytolysis but predominantly antibody-dependent phagocytosis. The cells have been shown to express cell-bound receptors for immunoglobulin and complement. J774 cells express high levels of the enzyme nitric oxide synthase and produce large amounts of nitric oxide when activated with IFN-gamma and a low concentration of bacterial lipopolysaccharides (10 ng/mL). Pretreatment of the cells with IL10 inhibits this process in a dose-dependent manner while addition of IL10 at the same time or after IFN-gamma activation is without effect. Treatment of J774 cells with IFN-gamma induces synthesis of IL12 mRNA expression. J774 is used in bioassays to detect M-CSF since its growth is dependent on this factor. The cells constitutively secrete IL1 into the conditioned medium. (http://www.copewithcytokines.de/cope.cgi?key=J774) J774 macrophage cell RAW 264.7 cell ATCC: TIB-71 RAW 264.7 disease: macrophage; AMLV-induced tumor Vero cell HyperCLDB: cl4644 Vero MeSH: D014709 ATCC: CCL-81 cell cell type cell A cell type is a distinct morphological or functional form of cell. Examples are epithelial, glial etc. A material entity of anatomical origin (part of or deriving from an organism) that has as its parts a maximally connected cell compartment surrounded by a plasma membrane. CALOHA:TS-2035 CL:0000000 EFO_URI: http://www.ebi.ac.uk/efo/EFO_0000324 FMA:68646 GO:0005623 KUPO:0000002 MO_548 The definition of cell is intended to represent all cells, and thus a cell is defined as a material entity and not an anatomical structure, which implies that it is part of an organism (or the entirety of one). VHOG:0001533 WBbt:0004017 XAO:0003012 cell epithelial, glial. Anatomical structure that has as its parts a maximally connected cell compartment surrounded by a plasma membrane. PMID:18089833.Cancer Res. 2007 Dec 15;67(24):12018-25. "...Epithelial cells were harvested from histologically confirmed adenocarcinomas .." cell epithelial cell A cell that is usually found in a two-dimensional sheet with a free surface. The cell has a cytoskeleton that allows for tight cell to cell contact and for cell polarity where apical part is directed towards the lumen and the basal part to the basal lamina. BTO:0000414 CALOHA:TS-2026 CARO:0000077 FBbt:00000124 FMA:66768 WBbt:0003672 cell epitheliocyte macrophage A mononuclear phagocyte present in variety of tissues, typically differentiated from monocytes, capable of phagocytosing a variety of extracellular particulate material, including immune complexes, microorganisms, and dead cells. BTO:0000801 CALOHA:TS-0587 FMA:63261 FMA:83585 Morphology: Diameter 30_M-80 _M, abundant cytoplasm, low N/C ratio, eccentric nucleus. Irregular shape with pseudopods, highly adhesive. Contain vacuoles and phagosomes, may contain azurophilic granules; markers: Mouse & Human: CD68, in most cases CD11b. Mouse: in most cases F4/80+; role or process: immune, antigen presentation, & tissue remodelling; lineage: hematopoietic, myeloid. cell histiocyte eukaryotic cell cell trophoblast cell A cell lining the outside of the blastocyst. After binding to the endometrium, trophoblast cells develop into two distinct layers, an inner layer of mononuclear cytotrophoblast cells and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblast cells, which form the early fetal-maternal interface. FMA:83028 cell trophoblastic cell dendritic cell A cell of hematopoietic origin, typically resident in particular tissues, specialized in the uptake, processing, and transport of antigens to lymph nodes for the purpose of stimulating an immune response via T cell activation. These cells are lineage negative (CD3-negative, CD19-negative, CD34-negative, and CD56-negative). BTO:0002042 CALOHA:TS-0194 FMA:83036 cell interdigitating cell veiled cell animal cell cell leukocyte An achromatic cell of the myeloid or lymphoid lineages capable of ameboid movement, found in blood or other tissue. leukocyte habitat A spatial region having environmental qualities which may sustain an organism or a community of organisms. habitat reproduction reproduction GO:0000003 GO:0019952 GO:0050876 The production of new individuals that contain some portion of genetic material inherited from one or more parent organisms. Wikipedia:Reproduction biological_process reproductive physiological process The production by an organism of new individuals that contain some portion of their genetic material inherited from that organism. reproduction adaptive immune response adaptive immune response An immune response based on directed amplification of specific receptors for antigen produced through a somatic diversification process, and allowing for enhanced response to subsequent exposures to the same antigen (immunological memory). GO:0002250 This term was added by GO_REF:0000022. Wikipedia:Adaptive_immune_system acquired immune response biological_process An immune response based on directed amplification of specific receptors for antigen produced through a somatic diversification process, and allowing for enhanced response to subsequent exposures to the same antigen (immunological memory). adaptive immune response leukocyte mediated immunity Any process involved in the carrying out of an immune response by a leukocyte. leukocyte mediated immunity chromosome A structure composed of a very long molecule of DNA and associated proteins (e.g. histones) that carries hereditary information. GO:0005694 Wikipedia:Chromosome cellular_component chromatid interphase chromosome prophase chromosome retrograde vesicle-mediated transport, Golgi to ER GO:0006890 GO:0048220 Reactome:REACT_101581 Reactome:REACT_106254 Reactome:REACT_107028 Reactome:REACT_110794 Reactome:REACT_11208 Reactome:REACT_33374 Reactome:REACT_78144 Reactome:REACT_78992 Reactome:REACT_79320 Reactome:REACT_84617 Reactome:REACT_84887 Reactome:REACT_86027 Reactome:REACT_86772 Reactome:REACT_87591 Reactome:REACT_88478 Reactome:REACT_88525 Reactome:REACT_92195 Reactome:REACT_92336 The directed movement of substances from the Golgi back to the endoplasmic reticulum, mediated by vesicles bearing specific protein coats such as COPI or COG. biological_process cis-Golgi to rough ER transport cis-Golgi to rough ER vesicle-mediated transport cis-Golgi to rough endoplasmic reticulum transport cis-Golgi to rough endoplasmic reticulum vesicle-mediated transport retrograde (Golgi to ER) transport retrograde transport, Golgi to ER retrograde transport, Golgi to endoplasmic reticulum retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum immune response immune response Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. GO:0006955 This term was improved by GO_REF:0000022. It was redefined and moved. biological_process Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. immune response humoral immune response An immune response mediated through a body fluid. humoral immune response tRNA processing GO:0008033 The process in which a pre-tRNA molecule is converted to a mature tRNA, ready for addition of an aminoacyl group. biological_process tRNA maturation biological_process biological_process Any process specifically pertinent to the functioning of integrated living units: cells, tissues, organs, and organisms. A process is a collection of molecular events with a defined beginning and end. GO:0000004 GO:0007582 GO:0008150 Note that, in addition to forming the root of the biological process ontology, this term is recommended for use for the annotation of gene products whose biological process is unknown. Note that when this term is used for annotation, it indicates that no information was available about the biological process of the gene product annotated as of the date the annotation was made; the evidence code ND, no data, is used to indicate this. Wikipedia:Biological_process biological process biological process unknown biological_process physiological process Any process specifically pertinent to the functioning of integrated living units: cells, tissues, organs, and organisms. A process is a collection of molecular events with a defined beginning and end. biological_process metabolic process GO:0008152 Note that metabolic processes do not include single functions or processes such as protein-protein interactions, protein-nucleic acids, nor receptor-ligand interactions. The chemical reactions and pathways, including anabolism and catabolism, by which living organisms transform chemical substances. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Wikipedia:Metabolism biological_process metabolic process resulting in cell growth metabolism metabolism resulting in cell growth cell death Any biological process that results in permanent cessation of all vital functions of a cell. A cell should be considered dead when any one of the following molecular or morphological criteria is met: (1) the cell has lost the integrity of its plasma membrane; (2) the cell, including its nucleus, has undergone complete fragmentation into discrete bodies (frequently referred to as "apoptotic bodies"); and/or (3) its corpse (or its fragments) have been engulfed by an adjacent cell in vivo. GO:0008219 accidental cell death biological_process necrosis death A permanent cessation of all vital functions: the end of life; can be applied to a whole organism or to a part of an organism. death immunoglobulin complex A protein complex that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains, held together by disulfide bonds and sometimes complexed with additional proteins. An immunoglobulin complex may be embedded in the plasma membrane or present in the extracellular space, in mucosal areas or other tissues, or circulating in the blood or lymph. immunoglobulin complex B cell receptor complex An immunoglobulin complex that is present in the plasma membrane of B cells and that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains and a signaling subunit, a heterodimer of the Ig-alpha and Ig-beta proteins. B cell receptor complex entry into host cell GO:0030260 Reactome:REACT_6903 The invasion by an organism of a cell of its host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. biological_process host cell invasion developmental process A biological process whose specific outcome is the progression of an integrated living unit: an anatomical structure (which may be a subcellular structure, cell, tissue, or organ), or organism over time from an initial condition to a later condition. developmental process macromolecular complex macromolecular complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which the constituent parts function together. GO:0032991 cellular_component macromolecule complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which the constituent parts function together. macromolecular complex entry of bacterium into host cell 2011-01-13T02:26:54Z GO:0035635 The process in which a bacterium enters a host cell. The host is defined as the larger of the organisms involved in a symbiotic interaction. bacterial entry into host cell biological_process invasion of bacteria into host cell rfoulger growth growth GO:0040007 GO:0048590 See also the biological process term 'cell growth ; GO:0016049'. The increase in size or mass of an entire organism, a part of an organism or a cell. biological_process growth pattern non-developmental growth The increase in size or mass of an entire organism, a part of an organism or a cell. growth T cell receptor complex A protein complex that contains a disulfide-linked heterodimer of T cell receptor (TCR) chains, which are members of the immunoglobulin superfamily, and mediates antigen recognition, ultimately resulting in T cell activation. The TCR heterodimer is associated with the CD3 complex, which consists of the nonpolymorphic polypeptides gamma, delta, epsilon, zeta, and, in some cases, eta (an RNA splice variant of zeta) or Fc epsilon chains. T cell receptor complex cytokinesis by binary fission A cytokinesis process that involves a set of conserved proteins including FtsZ, and results in the formation of two similarly sized and shaped cells; the process by which prokaryotic cells divide. cytokinesis by binary fission symbiosis, encompassing mutualism through parasitism An interaction between two organisms living together in more or less intimate association. The term host is usually used for the larger (macro) of the two members of a symbiosis. The smaller (micro) member is called the symbiont organism. Microscopic symbionts are often referred to as endosymbionts. The various forms of symbiosis include parasitism, in which the association is disadvantageous or destructive to one of the organisms; mutualism, in which the association is advantageous, or often necessary to one or both and not harmful to either; and commensalism, in which one member of the association benefits while the other is not affected. However, mutualism, parasitism, and commensalism are often not discrete categories of interactions and should rather be perceived as a continuum of interaction ranging from parasitism to mutualism. In fact, the direction of a symbiotic interaction can change during the lifetime of the symbionts due to developmental changes as well as changes in the biotic/abiotic environment in which the interaction occurs. symbiosis, encompassing mutualism through parasitism adhesion to host The attachment of an organism to its host via adhesion molecules, general stickiness etc., either directly or indirectly. The host is defined as the larger of the organisms involved in a symbiotic interaction. adhesion to host entry into host entry into host GO:0044409 Penetration by an organism into the body, tissues, or cells of the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. biological_process host invasion invasion into host invasion of host invasive growth Penetration by an organism into the body, tissues, or cells of the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. entry into host entry into host through host barriers Penetration by an organism into its host organism via active breaching of the physical barriers of the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. entry into host through host barriers interspecies interaction between organisms Any process in which an organism has an effect on an organism of a different species. GO:0044419 biological_process interaction with another species interspecies interaction interspecies interaction with other organisms innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. innate immune response intracellular transport GO:0046907 The directed movement of substances within a cell. biological_process negative regulation of viral reproduction Any process that stops, prevents, or reduces the frequency, rate or extent of the viral life cycle, the set of processes by which a virus reproduces and spreads among hosts. negative regulation of viral reproduction negative regulation of immune response Any process that stops, prevents, or reduces the frequency, rate or extent of the immune response, the immunological reaction of an organism to an immunogenic stimulus. negative regulation of immune response negative regulation of developmental process Any process that stops, prevents or reduces the rate or extent of development, the biological process whose specific outcome is the progression of an organism over time from an initial condition (e.g. a zygote, or a young adult) to a later condition (e.g. a multicellular animal or an aged adult). negative regulation of developmental process establishment of localization establishment of localization establishment of localization GO:0051234 The directed movement of a cell, substance or cellular entity, such as a protein complex or organelle, to a specific location. biological_process establishment of localisation Gene Ontology: http://purl.org/obo/owl/GO The directed movement of a cell, substance or cellular entity, such as a protein complex or organelle, to a specific location. establishment of localization establishment of localization in cell GO:0051649 The directed movement of a substance or cellular entity, such as a protein complex or organelle, to a specific location within, or in the membrane of, a cell. biological_process establishment of cellular localization establishment of intracellular localization establishment of localisation in cell establishment of localization within cell positioning within cell multi-organism process multi-organism process A biological process which involves another organism of the same or different species. GO:0051704 GO:0051706 biological_process interaction between organisms physiological interaction between organisms physiological interaction with other organism Any process by which an organism has an effect on another organism of the same or different species. multi-organism process nitric-oxide synthase biosynthetic process GO:0051767 GO:0051768 NO synthase biosynthesis NO synthase biosynthetic process NOS biosynthesis NOS biosynthetic process NOS1 biosynthesis NOS2 biosynthesis NOS2 synthase biosynthesis NOS2 synthase biosynthetic process NOS3 biosynthesis The chemical reactions and pathways resulting in the formation of a nitric-oxide synthase, an enzyme which catalyzes the reaction L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+. biological_process brain nitric-oxide synthase biosynthetic process endothelial nitric-oxide synthase biosynthetic process inducible nitric-oxide synthase biosynthetic process nitric-oxide synthase (type 2) biosynthesis nitric-oxide synthase (type 2) biosynthetic process nitric-oxide synthase (type II) biosynthesis nitric-oxide synthase (type II) biosynthetic process nitric-oxide synthase 2 biosynthetic process nitric-oxide synthase-1 biosynthetic process nitric-oxide synthase-2 biosynthetic process nitric-oxide synthase-3 biosynthetic process quorum sensing involved in interaction with host GO:0052106 The process in which a community of single-celled organisms living in intimate contact with a host organism monitors population density by detecting the concentration of small diffusible signal molecules. The host is defined as the larger of the organisms involved in a symbiotic interaction. biological_process quorum sensing during interaction with host biological regulation biological regulation Any process that modulates a measurable attribute of any biological process, quality or function. GO:0065007 biological_process regulation Any process that modulates the frequency, rate or extent of any biological process, quality or function. biological regulation reactive oxygen species metabolic process 2011-02-11T10:50:06Z GO:0072593 ROS metabolic process The chemical reactions and pathways involving a reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to biopolymers. biological_process midori reactive oxygen species metabolism mutualism An interaction between two organisms living together in more or less intimate association in a relationship in which both organisms benefit from each other. mutualism commensalism An interaction between two organisms living together in more or less intimate association in a relationship in which one benefits and the other is unaffected. commensalism phagosome maturation 2010-10-19T11:10:34Z A process that is carried out at the cellular level which results in the arrangement of constituent parts of a phagosome within a cell. Phagosome maturation begins with endocytosis and formation of the early phagosome and ends with the formation of the hybrid organelle, the phagolysosome. GO:0090382 biological_process tanyaberardini phagosome acidification 2010-10-27T10:20:22Z Any process that reduces the pH of the phagosome, measured by the concentration of the hydrogen ion. GO:0090383 biological_process phagosomal acidification tanyaberardini phagosome-lysosome fusion 2010-10-27T10:24:28Z GO:0090385 The creation of a phagolysosome from a phagosome and a lysosome. biological_process tanyaberardini objective specification Answers the question, why did you do this experiment? OBI Plan and Planned Process/Roles Branch OBI_0000217 PERSON: Alan Ruttenberg PERSON: Barry Smith PERSON: Bjoern Peters PERSON: Jennifer Fostel a directive information entity that describes an intended process endpoint. When part of a plan specification the concretization is realized in a planned process in which the bearer tries to effect the world so that the process endpoint is achieved. objective specification purpose of a study; support of hypothesis, discovery of new information action specification Alan Ruttenberg OBI Plan and Planned Process branch Pour the contents of flask 1 into flask 2 a directive information entity that describes an action the bearer will take data item 2009-03-16: data item deliberatly ambiguous: we merged data set and datum to be one entity, not knowing how to define singular versus plural. So data item is more general than datum. OBO:imported "http://purl.obolibrary.org/obo/iao.owl" 2/2/2009 Alan and Bjoern discussing FACS run output data. This is a data item because it is about the cell population. Each element records an event and is typically further composed a set of measurment data items that record the fluorescent intensity stimulated by one of the lasers. 2009-03-16: removed datum as alternative term as datum specifically refers to singular form, and is thus not an exact synonym. Data items include counts of things, analyte concentrations, and statistical summaries. PERSON: Alan Ruttenberg PERSON: Chris Stoeckert PERSON: Jonathan Rees a data item is an information content entity that is intended to be a truthful statement about something (modulo, e.g., measurement precision or other systematic errors) and is constructed/acquired by a method which reliably tends to produce (approximately) truthful statements. data data item symbol 20091104, MC: this needs work and will most probably change PERSON: Jonathan Rees a smallish, word-like datum... symbol information content entity OBO:sourced "OBI:0000142" Examples of information content entites include journal articles, data, graphical layouts, and graphs. OBI_0000142 PERSON: Chris Stoeckert an information content entity is an entity that is generically dependent on some artifact and stands in relation of aboutness to some entity information content entity directive information entity 8/6/2009 Alan Ruttenberg: Changed label from "information entity about a realizable" after discussions at ICBO An information content entity whose concretizations indicate to their bearer how to realize them in a process. PERSON: Alan Ruttenberg PERSON: Bjoern Peters Werner pushed back on calling it realizable information entity as it isn't realizable. However this name isn't right either. An example would be a recipe. The realizable entity would be a plan, but the information entity isn't about the plan, it, once concretized, *is* the plan. -Alan curation status specification Better to represent curation as a process with parts and then relate labels to that process (in IAO meeting) GROUP:OBI:<http://purl.obolibrary.org/obo/obi> OBI_0000266 PERSON:Bill Bug The curation status of the term. The allowed values come from an enumerated list of predefined terms. See the specification of these instances for more detailed definitions of each enumerated value. curation status specification data about an ontology part Person:Alan Ruttenberg data about an ontology part is a data item about a part of an ontology, for example a term plan specification 2009-03-16: provenance: a term a plan was proposed for OBI (OBI_0000344) , edited by the PlanAndPlannedProcess branch. Original definition was " a plan is a specification of a process that is realized by an actor to achieve the objective specified as part of the plan". It has been subsequently moved to IAO where the objective for which the original term was defined was satisfied with the definitionof this, different, term. Alan Ruttenberg Alternative previous definition: a plan is a set of instructions that specify how an objective should be achieved OBI Plan and Planned Process branch OBI_0000344 PMID: 18323827.Nat Med. 2008 Mar;14(3):226.New plan proposed to help resolve conflicting medical advice. a directive information entity that when concretized it is realized in a process in which the bearer tries to achieve the objectives, in part by taking the actions specified. Plan specifications includes parts such as objective specification, action specifications and conditional specifications. plan specification measurement datum 2/2/2009 is_specified_output of some assay? A measurement datum is an information content entity that is a recording of the output of a measurement such as produced by a device. Examples of measurement data are the recoding of the weight of a mouse as {40,mass,"grams"}, the recording of an observation of the behavior of the mouse {,process,"agitated"}, the recording of the expression level of a gene as measured through the process of microarray experiment {3.4,luminosity,}. OBI_0000305 group:OBI measurement datum person:Chris Stoeckert obsolescence reason specification PERSON: Alan Ruttenberg PERSON: Melanie Courtot The creation of this class has been inspired in part by Werner Ceusters' paper, Applying evolutionary terminology auditing to the Gene Ontology. The reason for which a term has been deprecated. The allowed values come from an enumerated list of predefined terms. See the specification of these instances for more detailed definitions of each enumerated value. obsolescence reason specification denotator type A denotator type indicates how a term should be interpreted from an ontological perspective. Alan Ruttenberg Barry Smith, Werner Ceusters The Basic Formal Ontology ontology makes a distinction between Universals and defined classes, where the formal are "natural kinds" and the latter arbitrary collections of entities. symbiont role Lindsay Cowell A role borne by an organism in symbiosis. The role is realized in symbiosis. Albert Goldfain Alexander Diehl mutualist role Alexander Diehl The role is realized in processes that result in the growth, survival, or fitness advantage of either organism. Lindsay Cowell Albert Goldfain A symbiont role borne by an organism in virtue of the fact that both symbionts derive a growth, survival, or fitness advantage from symbiosis. commensal role The role is realized in processes that result in the commensal's growth, survival, or fitness advantage. A symbiont role borne by an organism in virtue of the fact that it derives a growth, survival, or fitness advantage from symbiosis, but the other symbiont is neither advantaged nor disadvantaged. Albert Goldfain Lindsay Cowell Alexander Diehl parasite role Alexander Diehl In the medical community, the term 'parasite' is used with the narrower meaning of eukaryotic pathogen. A symbiont role borne by an organism in virtue of the fact that it derives a growth, survival, or fitness advantage from symbiosis while the other symbiont's growth, survival, or fitness is reduced. The role is realized in processes that result in the parasite's growth, survival, or fitness advantage or in the other organism's growth, survival, or fitness reduction. Albert Goldfain Lindsay Cowell infectious agent role A role borne by an infectious agent when contained in a host in which its infectious disposition can be realized. Albert Goldfain Lindsay Cowell Alexander Diehl pathogen role Alexander Diehl A role borne by pathogen in virtue of the fact that it or one of its products is sufficiently close to an organism towards which it has the pathogenic disposition to allow realization of the pathogenic disposition. Clostridium botulinum is an example of an entity with the capability to bear the pathogen role but that does not have the capability to bear the infectious agent role or the parasite role. The influenza viruses are examples of organisms that can bear both the infectious agent and pathogen roles. Albert Goldfain Lindsay Cowell opportunistic infectious disposition Albert Goldfain Alexander Diehl An infectious disposition to become part of a disorder only in organisms whose defenses are compromised. Lindsay Cowell The disposition is realized in a process by which the bearer becomes part of a disorder in an immunocompromised host. This includes individuals who are immunocompromised or who have damaged barriers that normally protect against infection (e.g. skin). opportunitistic pathogenic disposition primary infectious disposition A pathogen with a primary infectious disposition can cause disease or death in both immunocompromised and immunocompetent hosts. Lindsay Cowell A quote from page 3 of Mandell's "Principles and Practice of Infectious Diseases" (Sixth edition): "It is useful to distinguish "principal" pathogens, which regularly cause disease in some proportion of susceptible individuals with apparently intact defense systems, from other potentially pathogenic microorganisms. ... even for most organisms classified as principal pathogens, for example, Staphylococcus aureus and the pneumococcus, some impairment or local breakdown in normal host defense mechanisms must occur for these bacteria to cause disease. ... Thus, it seems clear that the capacity of certain microorganisms to cause disease in seemingly uncompromised human hosts on a regular basis reflects some fundamental difference in their virulence capabilities from those of opportunists and the more numerous commensal species that rarely, if ever, cause disease." Albert Goldfain Alexander Diehl An infectious disposition to become part of a disorder in organisms that have intact defenses. symbiont host role A host role borne by an organism in virtue of the fact that its extended organism contains a second organism and provides an environment supportive for the survival, growth, maturation, or reproduction of that organism. Alexander Diehl Lindsay Cowell The relevant environmental resources may include nutrient resources, warmth, or moisture. The role is realized in processes in which the host makes the relevant environmental resources available to its partner in symbiosis. A bearer of a symbiont host role is bearer also of a symbiont role. Albert Goldfain definitive host role Lindsay Cowell A symbiont host role borne by an organism in virtue of the fact that its partner in symbiosis reaches developmental maturity or reproduces sexually in the host. The role is realized in developmental and reproduction processes of the host's partner in symbiosis. Albert Goldfain Alexander Diehl primary host role intermediate host role A symbiont host role borne by an organism in virtue of the fact that its partner in symbiosis utilizes the host to undergo a developmental stage transition, and the host is required for continuation of the partner's life cycle. Albert Goldfain The role is realized in developmental processes of the host's partner in symbiosis. Alexander Diehl Lindsay Cowell secondary host role paratenic host role A symbiont host role borne by an organism in virtue of the fact that its partner in symbiosis utilizes the host to undergo a developmental stage transition, but the host is not required for continuation of the partner's life cycle. Lindsay Cowell The role is realized in developmental processes of the host's partner in symbiosis. Albert Goldfain Alexander Diehl dead-end host role Alexander Diehl A symbiont host role borne by an organism in virtue of the fact that its partner in symbiosis has the infectious disposition but cannot be transmitted from the host to the partner's definitive host. Lindsay Cowell Albert Goldfain incidental host role parasite host role Albert Goldfain The role is realized in processes that result in the parasite's growth, survival, or fitness advantage or in the host's growth, survival, or fitness reduction. Lindsay Cowell The partner in symbiosis bears the parasite role. Alexander Diehl A symbiont host role borne by an organism in virtue of the fact that its partner in symbiosis derives from the host a growth, survival, or fitness advantage while the host's growth, survival, or fitness is reduced. infectious agent host role Alexander Diehl By this definition, vectors and other organisms that may not be infected are bearers of the infectious agent host role. A pathogen host role borne by an organism in virtue of the fact that its extended organism contains an infectious agent. Albert Goldfain Lindsay Cowell pathogen host role Albert Goldfain A host role borne by an organism in virtue of the fact that its extended organism contains a pathogen. Lindsay Cowell Bearing the infectious agent host role implies bearing the pathogen host role, but the reverse is not true. See comment for infectious agent host role. Alexander Diehl infectious agent carrier role Alexander Diehl Albert Goldfain An infectious agent host role borne by an organism in virtue of the fact that its extended organism contains an infectious agent, the infectious agent has the infectious disposition towards the host, and the host has no symptoms of the infectious disease caused by the infectious agent. Lindsay Cowell infectious agent transporter role Albert Goldfain Alexander Diehl The role is realized in a process that transfers an infectious organism from one location to another. Lindsay Cowell A role borne by a material entity in virtue of the fact that an infectious agent is located in or on the entity and the entity has the capability to transfer (either actively or passively) the infectious agent from one location to another. infectious agent vector role Lindsay Cowell The role is realized in a transmission process. A bearer of a vector role is also a bearer of a host role. Albert Goldfain Alexander Diehl An infectious agent transporter role that is borne by an organism active in the transfer of an infectious agent to an organism of another Species and in which the agent is infectious. mechanical vector of infectious agent role Alexander Diehl An infectious agent vector role borne by an organism in virtue of the fact that the infectious agent does not multiply in or on the vector. Lindsay Cowell Albert Goldfain biological vector of infectious agent role Lindsay Cowell Albert Goldfain Alexander Diehl An infectious agent vector role borne by an organism in virtue of the fact that the infectious agent multiplies in or on the vector. infectious agent vehicle role Albert Goldfain Alexander Diehl Lindsay Cowell An infectious agent transporter role borne by an entity in virtue of the fact that the entity is not a complete organism. Drinking water bears the infectious agent vehicle role, but does not bear either of the subtype roles. biological vehicle of infectious agent role An infectious agent vehicle role borne by an entity in virtue of the fact that the entity is living or contains living cells other than those that have the infectious disposition. Lindsay Cowell Albert Goldfain Examples include blood, serum, tissue, or fresh produce. Alexander Diehl fomite role Alexander Diehl Lindsay Cowell Albert Goldfain An infectious agent vehicle role borne by an entity in virtue of the fact that the entity is not alive. reservoir of infectious agent role A role borne by a material entity in virtue of the fact that it is a habitat in which infectious agents can persist and multiply and from which they can be transmitted in virtue of prevailing practices of potential hosts. Albert Goldfain Lindsay Cowell Alexander Diehl The role is realized in a process that has as part life and multiplication processes of an infectious agent and a transmission process. If the material entity bearing the reservoir role is an organism, then this organism also bears the host role. The organism may also bear the vector role. virulence factor disposition The virulence factor disposition is typically realized in processes that improve survival of the pathogen in a host, increase the likelihood of transmission to a host, or cause pathological processes in a host. Albert Goldfain A disposition borne by a biological macromolecule produced by a pathogen that is a disposition to undergo processes that increase the pathogen's virulence. Lindsay Cowell Alexander Diehl toxin disposition Albert Goldfain Lindsay Cowell Alexander Diehl A disposition to cause I) malfunction of cells, ii) damage to extracellular matrix, or iii) damage of cells to a degree that can result in cell death. exotoxin disposition Alexander Diehl The disposition is realized in a direct enzymatic process that damages host cells or extracellular matrix. Albert Goldfain Lindsay Cowell A toxin disposition to damage cells or extracellular matrix by a direct enzymatic process. infectious agent portal of entry role Albert Goldfain A role borne by an anatomical entity in virtue of the fact that it serves as the site through which an infectious agent enters a host. Lindsay Cowell Alexander Diehl The role is realized in a process by which an infectious agent enters a host. infectious agent portal of exit role Lindsay Cowell A role borne by an anatomical entity in virtue of the fact that it serves as the site through which an infectious agent exits a host. Alexander Diehl Albert Goldfain The role is realized in a process by which an infectious agent exists a host. disinfectant role Lindsay Cowell The role is realized in the killing and/or growth inhibition of microorganisms on the non-living entity. A role borne by a material entity in virtue of the fact that it has an antimicrobial disposition and is applied to a non-living entity. Alexander Diehl Albert Goldfain antiseptic role The role is realized in the killing and/or growth inhibition of microorganisms on the anatomical entity. A role borne by a material entity in virtue of the fact that it has an antimicrobial disposition and is applied to an anatomical entity of a living organism. Lindsay Cowell Albert Goldfain Alexander Diehl primary infection role Alexander Diehl A role borne by an infectious disorder in virtue of the fact that (1) the host has at least two distinct infectious disorders, where neither arose from the other through metastasis, (2) at the time the infectious disorder was established in the host, the host had no infectious disorder, and (3) the infectious disorder increases the host's susceptibility to infectious disorders. Lindsay Cowell Albert Goldfain The role is realized in a process by which the infectious disorder is established in the host. secondary infection role The role is realized in a process by which the infectious disorder is established in the host. Lindsay Cowell Albert Goldfain A role borne by an infectious disorder in virtue of the fact that (1) the host has at least two distinct infectious disorders, where neither arose from the other through metastasis, (2) at the time the infectious disorder was established in the host, the host had a primary infectious disorder, and (3) establishment of the infectious disorder occurs because of increased susceptibility to infectious disorders conferred by the primary infectious disorder. Alexander Diehl infectious disease The disposition is realized in an infectious disease course. Alexander Diehl Lindsay Cowell Albert Goldfain A disease whose physical basis is an infectious disorder. tranmissible disease adhesion disposition The disposition is realized in an adherence to host process. A disposition borne by a biological macromolecule that is the disposition to participate in adherence to host. Albert Goldfain Lindsay Cowell Alexander Diehl invasion disposition Alexander Diehl A molecule with the invasion disposition is referred to as an invasion factor or invasin. A disposition borne by a biological macromolecule that is the disposition to facilitate breach of host epithelial barriers or entry into and survival in host cells. Albert Goldfain Lindsay Cowell antimicrobial disposition Alexander Diehl Albert Goldfain The disposition is realized in the killing or growth inhibition of microorganisms. Some instances might be functions, depending on whether the bearer is something that exists and is used for the purpose (alcohol) or something that was designed for the purpose (pine sol). Entities that kill microorganisms are referred to as microbicidal; entities that inhibit the growth of microorganisms are referred to as microbistatic. Lindsay Cowell A disposition to kill or inhibit the development or reproduction of microorganisms. antiviral disposition A disposition to kill or inhibit the lifecycle of viruses. Alexander Diehl Albert Goldfain Lindsay Cowell antifungal disposition Albert Goldfain Lindsay Cowell Alexander Diehl A disposition to kill or inhibit the development or reproduction of fungal organisms. antibacterial disposition Lindsay Cowell antibiotic disposition A disposition to kill or inhibit the reproduction of bacteria. Albert Goldfain Alexander Diehl antiparasitic disposition A disposition to kill or inhibit the development or reproduction of eukaryotic parasites. Lindsay Cowell Alexander Diehl Albert Goldfain In the term name, we are using parasite in the medical sense of eukaryotic organisms that are parasitic in humans. protective resistance Lindsay Cowell Albert Goldfain The disposition is realized in a process that mitigates damage to the bearer and has the part as a participant. Alexander Diehl This mitigation sometimes takes the form of protection. CCR5 mutations protect T cells from HIV invasion. If a patient's tumor is resistant to chemotherapy, then the patient is resistant to something beneficial, but the tumor is resistant to something damaging. In this case protective resistance inheres in the tumor's cells and in the tumor, but not in the patient. In some cases, the quality that confers the protective resistance will confer other dispositions that damage the entity, such as is the case with sickle cell trait. A disposition that inheres in a material entity in virtue of the fact that the entity has a part (e.g. a gene product), which itself has a disposition to mitigate damage to the entity. resistance to drug Alexander Diehl A protective resistance that mitigates the damaging effects of a drug. Lindsay Cowell Albert Goldfain drug resistance resistance to infectious agent Lindsay Cowell Albert Goldfain Alexander Diehl A protective resistance that inheres in an organism and mitigates the damaging effects on that organism of an infectious agent. herd immunity to infectious organism A collective resistance disposition that inheres in an organism population in virtue of the fact that the proportion of the population with immunity to an infectious agent is high resulting in a low number of transmissions from hosts in the population to susceptible individuals in the population and thereby mitigating the damaging effects of the infectious agent on the population. Alexander Diehl Lindsay Cowell Albert Goldfain immunity to infectious agent Albert Goldfain We don't specify that immunity results from prior exposure, because we want to include innate immunity. In addition, for adaptive immunity, there could be some low level immunity even in a primary immune response. Lindsay Cowell A resistance to infectious agent that inheres in an organism in virtue of immune system components in the extended organism. Alexander Diehl protective immunity to infectious agent sterilizing immunity to infectious agent Alexander Diehl Albert Goldfain An immunity to infectious agent that results in elimination of the infectious agent from the host. Sterilizing immunity is typically conferred by neutralizing antibodies. Lindsay Cowell pathogenic disposition A disposition to initiate processes that result in a disorder. The use of 'initiates' is intended to convey that a pathogenic disposition is realized when processes resulting in a disorder begin because of some action on the part of the bearer of the disposition. By this interpretation of 'initiates', disorder-causing entities such as glass, UV light, and toxins do not have a pathogenic disposition. The disposition is realized in processes that create a disorder. Albert Goldfain Lindsay Cowell Alexander Diehl pathogenicity invasive disposition Alexander Diehl A disposition borne by an infectious agent that is the disposition to penetrate the epithelial barriers of an organism of another Species. Lindsay Cowell Albert Goldfain infectious disposition Albert Goldfain A pathogenic disposition that inheres in an organism and is the disposition for that organism (1) to be transmitted to a host, (2) to establish itself in the host, and (3) to become part of a disorder in the host. Lindsay Cowell The disposition is realized in a process that has as part a transmission process, an establishment in host process, and a process in which an entity becomes part of a disorder. The infectious disposition has a complementary disposition that inheres in an organism and is the capability to be host to an entity with an infectious disposition and to undergo processes intiated by that entity that result in a disorder. Alexander Diehl zoonotic disposition Albert Goldfain Alexander Diehl An infectious disease associated with an infectious agent that bears the zoonotic disposition is referred to as a zoonosis. An infectious disposition that is the disposition to be transmitted from an infected, non-human host to a human host. Lindsay Cowell reverse zoonotic disposition Alexander Diehl Albert Goldfain Lindsay Cowell An infectious disease associated with an infectious agent that bears the reverse zoonotic disposition is referred to as a reverse zoonosis. An infectious disposition that is the disposition to be transmitted from an infected, human host to a non-human host. collective disposition "... in virtue of the individual dispositions of the contstituents" is intended to capture the fact that the collective disposition results from the combination of the individual dispositions. It is not necessary that every constituent of the aggregate have a relevant individual disposition. Albert Goldfain Alexander Diehl A disposition that inheres in a collection of entities in virtue of the individual dispositions of the constituents of that collection. The disposition is realized in a process that has as part realizations of some of the individual dispositions. Lindsay Cowell immunosuppressed organism Alexander Diehl An organism that is experiencing pregnancy-induced or pathologic immunosuppression. Lindsay Cowell Albert Goldfain immunocompetent organism Albert Goldfain An organism that has immunocompetence. Lindsay Cowell Alexander Diehl contagiousness Lindsay Cowell Albert Goldfain A disposition that inheres in a host of infectious agent and is a disposition to transmit infectious agents to organisms of the same Species through casual contact with a high likelihood of realization. The disposition is realized in a horizontal transmission process. Highly contagious infections, those with a relatively high likelihood of spread, are referred to as contagious and are those for which spread is likely as a result of data-to-day activities of the host. Alexander Diehl colonized host Albert Goldfain Lindsay Cowell Alexander Diehl An organism that contains a colony in or on its extended organism. infected organism Lindsay Cowell Alexander Diehl Albert Goldfain An organism that has an infection in or on its extended organism. co-infected organism Albert Goldfain Lindsay Cowell Alexander Diehl An organism that has two infections with distinct Species of infectious agents. infectious agent transmissibility The transmissibility quality varies with both the type of organism being transmitted and the type of organism to which transmission is happening. Albert Goldfain Lindsay Cowell A quality that inheres in an infectious agent and is the likelihood that the infectious agent will undergo a horizontal transmission process. Alexander Diehl infectivity This quality is measured by the proportion of exposed who become infected. Alexander Diehl A quality that inheres in an infectious agent and is the liklihood that the infectious disposition will be realized upon exposure of a susceptible organism. Albert Goldfain Lindsay Cowell virulence This quality is measured by the proportion of clinically apparent cases that are severe or fatal. Albert Goldfain Alexander Diehl A quality that inheres in an infectious agent and is the degree to which realizations of the infectious disease caused by the infectious agent become severe or fatal. Lindsay Cowell susceptibility Low susceptibility is often referred to as resistance. In this sense, resistance is a quality. Alexander Diehl Lindsay Cowell A quality that inheres in an entity and is the degree to which it can be harmed by another entity. Albert Goldfain susceptibility to infectious agent Albert Goldfain A susceptibility that inheres in an organism and is the degree to which it can be harmed by an infectious agent. Lindsay Cowell Alexander Diehl drug susceptibility Lindsay Cowell Alexander Diehl Albert Goldfain A susceptibility that is the degree to which an entity can be harmed or inhibited from surviving by a drug. drug susceptibility of infectious agent Albert Goldfain A drug susceptibility that inheres in an infectious agent and is the degree to which the infectious agent can be harmed or inhibited from surviving by a drug. Alexander Diehl Lindsay Cowell complex infection Lindsay Cowell Alexander Diehl Albert Goldfain DL needs 'different species' An infection comprised of infectious organisms from different Species. mixed infection polymicrobial infection extracellular infection Albert Goldfain Lindsay Cowell Alexander Diehl An infection for which the infectious agents that are part of the infection persist in the extracellular space of the host. intracellular infection Lindsay Cowell Alexander Diehl Albert Goldfain An infection for which the infectious agents that are part of the infection persist inside host cells. systemic infection Albert Goldfain Lindsay Cowell An infection for which the infectious agents that are part of the infection are distributed throughout the host. DL needs 'distributed throughout' Alexander Diehl local infection Alexander Diehl Albert Goldfain An infection for which the infectious agents that are part of the infection are limited to a relatively small area of the host's body. DL needs 'relatively small area' Lindsay Cowell focal infection Alexander Diehl Albert Goldfain A local infection for which symptoms are observed in parts of the host's extended organism that are distant from the infection. Lindsay Cowell acute infectious disease course Albert Goldfain Alexander Diehl Lindsay Cowell An infectious disease course that begins soon after infection is established and progresses rapidly to severe stages. infectious disease incidence A quality that inheres in an organism population and is the number of realizations of an infectious disease for which the infectious disease course begins during a specified period of time. Albert Goldfain A particular instance of infectious disease incidence will depend on a type of infectious disease, a population, and a period of time. Incidence is used as a measure of risk. Actual measures of incidence are based only on reported cases and usually specify a time interval and geographic location. Other constraints may include population demographics. These constraints will vary with the context of the incidence measure. Lindsay Cowell Alexander Diehl infection incidence Alexander Diehl A particular instance of infection incidence will depend on a type of infectious agent, a population, and a period of time. Incidence is used as a measure of risk. Actual measures of incidence are based only on reported cases and usually specify a time interval and geographic location. Other constraints may include population demographics. These constraints will vary with the context of the incidence measure. Lindsay Cowell Albert Goldfain A quality that inheres in an organism population and is the number of organisms in the population that become infected with an infectious agent during a specified period of time. infectious disease incidence proportion Albert Goldfain A quality that inheres in an organism population and is the proportion of members of the population not experiencing an infectious disease course at the beginning of a specified period of time in whom the infectious disease begins during the specified period of time. Alexander Diehl An instance of infectious disease incidence proportion is measured by dividing a measure of an instance of infectious disease incidence by the number of members of the population in which the infectious disease course had not begun at the beginning of the specified period of time over which the incidence was measured. Lindsay Cowell cumulative incidence of infectious disease infection incidence proportion Lindsay Cowell Alexander Diehl Albert Goldfain An instance of infection incidence proportion is measured by dividing a measure of an instance of infection incidence by the number of members of the population not infected at the beginning of the specified period of time over which the incidence was measured. A quality that inheres in an organism population and is the proportion of members of the population not experiencing an infectious disease course at the beginning of a specified period of time in whom the infectious disease begins during the specified period of time. cumulative incidence of infection infectious disease incidence rate Albert Goldfain An instance of infectious disease incidence rate is measured by dividing a measure of an instance of the infectious disease incidence proportion by the length of the period of time over which the incidence was measured. A quality that inheres in an organism population and is the infectious disease incidence proportion per unit time. Lindsay Cowell Alexander Diehl infection incidence rate An instance of infection incidence rate is measured by dividing a measure of an instance of infection incidence proportion by the length of the period of time over which the incidence was measured. Lindsay Cowell Alexander Diehl A quality that inheres in an organism population and is the infection incidence proportion per unit time. Albert Goldfain infectious disease prevalence Prevalence is sometimes defined as a proportion with total population size in the denominator. A particular instance of infectious disease prevalence will depend on a type of infectious disease, a population, and a period of time. Actual measures of prevalence are based only on reported cases and usually specify a time interval and geographic location. Other constraints may include population demographics. Albert Goldfain Lindsay Cowell A quality that inheres in an organism population and is the number of realizations of an infectious disease in the population at a specified time. Alexander Diehl infection prevalence A quality that inheres in an organism population and is the number of organisms in the population infected with an infectious agent at a specified time. Alexander Diehl Prevalence is sometimes defined as a proportion with total population size in the denominator. A particular instance of infection prevalence will depend on a type of infectious agent, a population, and a period of time. Actual measures of prevalence are based only on reported cases and usually specify a time interval and geographic location. Other constraints may include population demographics. Albert Goldfain Lindsay Cowell infectious disease lifetime prevalence Alexander Diehl Lindsay Cowell Albert Goldfain A quality that inheres in an organism population and is the number of organisms in the population who have, at any point during their lives, been bearers of an infectious disease and experienced realization of the disease. Prevalence is sometimes defined as a proportion with total population size in the denominator. A particular instance of infectious disease lifetime prevalence will depend on a type of infectious disease and a population. Actual measures of prevalence are based only on reported cases and usually specify a geographic location. Other constraints may include population demographics. infectious agent seroprevalence Albert Goldfain A quality that inheres in an organism population and is the number of organisms in the population that have antibody specific for an infectious agent in their serum at a specified time. Prevalence is sometimes defined as a proportion with total population size in the denominator. A particular instance of infectious agent seroprevalence will depend on a type of infectious agent and a population. Actual measures of seroprevalence are based only on tested individuals and usually specify a geographic location. Other constraints may include population demographics. Alexander Diehl Lindsay Cowell infectious disease mortality rate Alexander Diehl A quality that inheres in an organism population and is the per capita number of deaths in the population resulting from an infectious disease over a specified period of time. Lindsay Cowell A particular instance of infectious disease mortality rate will depend on a type of infectious disease and a population. Actual measures of mortality rate are based only on reported cases and usually specify a geographic location. Other constraints may include population demographics. Mortality rate is typically expressed in units of deaths per 1000 individuals per year. Albert Goldfain infectious disease endemicity Alexander Diehl A particular instance of infectious disease endemicity will depend on a type of infectious agent and a population. The population may be specified by temporal, geographic, or demographic constraints. Infectious diseases that are typical or common to a particular population are referred to as endemic. A quality that inheres in an organism population in virtue of the fact that infections of the type that causes an infectious disease are maintained in the population via intra-population transmission or by transmission from a local reservoir. Lindsay Cowell Albert Goldfain infectious disease endemic level Alexander Diehl An infectious disease prevalence that is typical for an infectious disease in an organism population. Infectious disease endemic level is relational to previous prevalences of the disease. Lindsay Cowell Albert Goldfain infectious disease endemic rate Albert Goldfain Alexander Diehl An infectious disease incidence rate that is typical for an infectious disease in an organism population. Infectious disease endemic rate is relational to previous infectious disease incidence rates of the disease. Lindsay Cowell infectious disease hyper-endemicity Hyper-endemic infectious diseases may have high endemic levels only in certain seasons. A hyper-endemic disease affects all age groups equally. Lindsay Cowell Alexander Diehl Albert Goldfain An infectious disease endemicity that inheres in an organism population in virtue of the fact that the infectious disease endemic level for an infectious disease is persistently high in the population. infectious disease sporadicity Albert Goldfain A quality that inheres in an organism population by virtue of the fact that realizations of an infectious disease occur in the population with a fluctuating prevalence. Lindsay Cowell Alexander Diehl Sporadic quality of infectious disease is relational to previous prevalence of the disease. infectious disease course Lindsay Cowell Alexander Diehl A disease course that is the realization of an infectious disease. Albert Goldfain long-term non-progressing infectious disease course Alexander Diehl Albert Goldfain Lindsay Cowell A chronic infectious disease course that does not progress to severe stages for a long period of time. immunization against infectious agent A process by which an organism acquires immunity to an infectious agent. Alexander Diehl Lindsay Cowell Albert Goldfain active immunization against infectious agent Lindsay Cowell Albert Goldfain Alexander Diehl An immunization that begins with exposure of an organism to antigen and results in immunity against an infectious agent. inoculation vaccination against infectious agent Albert Goldfain Alexander Diehl An active immunization that begins with exposure of an organism to a vaccine. Lindsay Cowell variolation Alexander Diehl Lindsay Cowell Albert Goldfain An active immunization that begins with exposure to smallpox in the form of a scab from a pustule and results in immunity against smallpox. passive immunization against infectious agent Albert Goldfain An immunization that begins with transfer to an organism of molecules not produced by that organism and that confer immunity against an infectious agent. Lindsay Cowell Alexander Diehl Examples include the injection of antibodies and the transfer of maternal antibodies to the fetus. infectious disease epidemic A process of infectious disease realizations and for which there is a statistically significant increase in the infectious disease incidence of a population. For a particular instance of infectious disease epidemic, signficance is determined based on the infectious disease incidence that is typical for an infectious disease for the particular population and time period. Lindsay Cowell Alexander Diehl Albert Goldfain infectious disease outbreak infectious disease pandemic A process in which multiple infectious disease epidemics of the same type of infectious disease unfold over overlapping periods of time and affect organism populations located in different geographic regions, including different countries and continents. Albert Goldfain Lindsay Cowell Alexander Diehl infectious disorder Lindsay Cowell Alexander Diehl Albert Goldfain An infection that is clinically abnormal. viremia Alexander Diehl Albert Goldfain An infection that has as part virus particles located in the blood. Lindsay Cowell DL needs FMA term. bacteremia Alexander Diehl Albert Goldfain An infection that has as part bacteria located in the blood. DL needs FMA term. Lindsay Cowell virion A virus that is in its assembled state consisting of genomic material (DNA or RNA) surrounded by coating molecules. Albert Goldfain Melanie Courtot Alexander Diehl Lindsay Cowell organism population Lindsay Cowell The organism population may be delineated by spatio-temporal proximity or by demographic criteria such as age. Alexander Diehl Albert Goldfain An aggregate of organisms of the same Species. infected population Alexander Diehl Lindsay Cowell Albert Goldfain An organism population whose members have an infection. diseased population Albert Goldfain An organism population in whose members an infectious disease is being realized. Lindsay Cowell Alexander Diehl infectious agent population Lindsay Cowell Alexander Diehl Albert Goldfain An organism population whose members each have an infectious disposition. susceptible population Albert Goldfain Lindsay Cowell Alexander Diehl An organism population whose members are not infected with an infectious agent and who lack immunity to the infectious agent. at-risk population normal resident microbiota population Lindsay Cowell Alexander Diehl Albert Goldfain An organism population whose members are particpating in non-parasitic symbiosis with a particular host. normal resident microflora population incubation period Albert Goldfain Alexander Diehl Lindsay Cowell A continuous temporal interval beginning with the extablishment of an infectious agent colony and ending with the onset of symptoms (or infectious disease course?). communicability period Alexander Diehl Lindsay Cowell Albert Goldfain A continuous temporal interval during which contagiousness inhering in the bearer of a host role. symbiont Alexander Diehl Lindsay Cowell Albert Goldfain An organism bearing a symbiont role. obligatory symbiont Albert Goldfain Lindsay Cowell Alexander Diehl An organism that can only reach developmental maturity, replicate, or persist in symbiosis. mutualist Lindsay Cowell Alexander Diehl Albert Goldfain An organism bearing a mutualist role. commensal Albert Goldfain Lindsay Cowell Alexander Diehl An organism bearing a commensal role. parasite Lindsay Cowell A organism bearing a parasite role. Alexander Diehl Albert Goldfain pathogen A material entity with a pathogenic disposition. Alexander Diehl Lindsay Cowell Albert Goldfain primary pathogen Alexander Diehl principal pathogen Lindsay Cowell Albert Goldfain An infectious agent with a primary infectious disposition. host Lindsay Cowell Albert Goldfain Alexander Diehl An organism bearing a host role. definitive host Albert Goldfain Alexander Diehl An organism bearing a definitive host role. Lindsay Cowell primary host intermediate host Lindsay Cowell Albert Goldfain A organism bearing an intermediate host role. Alexander Diehl secondary host paratenic host Alexander Diehl Albert Goldfain Lindsay Cowell An organism bearing a paratenic host role. dead-end host Lindsay Cowell Albert Goldfain Alexander Diehl An organism bearing a dead-end host role. incidental host parasite host Alexander Diehl Albert Goldfain An organism bearing a parasite host role. Lindsay Cowell infectious agent host Lindsay Cowell Alexander Diehl Albert Goldfain An organism bearing an infectious agent host role. pathogen host Lindsay Cowell Albert Goldfain Alexander Diehl An organism bearing a pathogen host role. infectious agent carrier Alexander Diehl An organism bearing the infectious agent carrier role. Lindsay Cowell Albert Goldfain infectious agent vector Alexander Diehl Albert Goldfain An organism bearing an infectious agent vector role. Lindsay Cowell mechanical vector of infectious agent Alexander Diehl Lindsay Cowell Albert Goldfain An infectious agent vector bearing a mechanical vector of infectious agent role. biological vector of infectious agent Lindsay Cowell Albert Goldfain Alexander Diehl An infectious agent vector bearing a biological vector of infectious agent role. vehicle of infectious agent Albert Goldfain Alexander Diehl Lindsay Cowell A material entity bearing an infectious agent vehicle role. fomite Lindsay Cowell A material entity bearing a fomite role. Albert Goldfain Alexander Diehl infectious agent reservoir A material entity bearing an infectious agent reservoir role. Albert Goldfain Alexander Diehl Lindsay Cowell virulence factor Alexander Diehl Albert Goldfain Lindsay Cowell DL: Needs 'product of' relation. It is a product of this process: production and has_participant some (has_role some pathogen and has_disposition some 'virulence factor disposition') A biological macromolecule produced by a pathogen and that has a virulence factor disposition. invasion factor Lindsay Cowell Alexander Diehl Albert Goldfain A biological macromolecule that has an invasion disposition. invasin toxin Lindsay Cowell Albert Goldfain A molecular entity that has a toxin disposition. Alexander Diehl exotoxin Lindsay Cowell Alexander Diehl A molecular entity bearing an exotoxin disposition. Albert Goldfain enterotoxin Alexander Diehl Albert Goldfain Lindsay Cowell A molecular entity with an exotoxin disposition, the realization of which damages cells of the host intestinal mucosa. endotoxin Alexander Diehl Lindsay Cowell A molecular entity with a toxin disposition and that is a structural component of a pathogen and is released from the pathogen only upon cytolysis. IDO Error endotoxin role => endotoxin disposition Albert Goldfain infectious agent portal of entry Lindsay Cowell Albert Goldfain Alexander Diehl An anatomical entity bearing an infectious agent portal of entry role. infectious agent portal of exit Alexander Diehl Lindsay Cowell Albert Goldfain An anatomical entity bearing an infectious agent portal of exit role. disinfectant Lindsay Cowell Albert Goldfain A material entity bearing a disinfectant role. Alexander Diehl antiseptic Alexander Diehl A material entity bearing an antiseptic role. Albert Goldfain Lindsay Cowell adhesion factor A biological macromolecule that has an adhesion disposition. Albert Goldfain Lindsay Cowell Alexander Diehl adhesin adhesion molecule antimicrobial Alexander Diehl A material entity with an antimicrobial disposition. Albert Goldfain Lindsay Cowell antiviral Albert Goldfain Lindsay Cowell Alexander Diehl A material entity bearing an antiviral disposition. antifungal Alexander Diehl A material entity bearing an antifungal disposition. Albert Goldfain Lindsay Cowell antiparasitic Albert Goldfain A material entity bearing an antiparasitic disposition. Lindsay Cowell Alexander Diehl antibiotic Alexander Diehl A material entity bearing an antiviral disposition. Albert Goldfain Lindsay Cowell microbicide DL needs 'process of killing microorganisms' Albert Goldfain Alexander Diehl Lindsay Cowell A material entity with an antimicrobial disposition that is realized in a process of killing microorganisms. microbicidal [entity] viricide Lindsay Cowell Albert Goldfain DL needs 'process of killing viruses' Alexander Diehl A material entity with an antiviral disposition that is realized in a process of killing viruses. microbistatic A material entity with an antimicrobial disposition that is realized in a process of inhibiting the growth of microorganisms. Alexander Diehl Lindsay Cowell DL needs 'process of inhibiting the growth of microorganisms' Albert Goldfain primary infection Lindsay Cowell Albert Goldfain Alexander Diehl An infection bearing the primary infection role. secondary infection Alexander Diehl Albert Goldfain An infection bearing the secondary infection role. Lindsay Cowell zoonosis Albert Goldfain Lindsay Cowell Alexander Diehl An infectious disease that has as its physical basis an infectious disorder composed of infectious agents that have a zoonotic disposition. aymptomatic host of infectious agent Alexander Diehl Albert Goldfain Lindsay Cowell An organism that is host to an infectious agent has no symptoms of the infectious disease associated with the infectious agent. subclinical infection Albert Goldfain Lindsay Cowell Alexander Diehl An infection that is part of an asymptomatic host. resistant entity Alexander Diehl A material entity that has a resistance disposition. Albert Goldfain Lindsay Cowell chronic carrier of infectious agent Albert Goldfain An organism who has been bearer of the infectious agent carrier role for an extended period of time. Lindsay Cowell Alexander Diehl symptomatic host of infectious agent Alexander Diehl Albert Goldfain An organism who is host to an infectious agent and has symptoms of the infectious disease associated with the infectious agent Lindsay Cowell innate immunity to infectious agent The disposition is realized in an innate immune response. Alexander Diehl Lindsay Cowell Albert Goldfain An immunity to infectious agent that inheres in an organism in virtue of germline encoded components that directly recognize components of potential pathogens. humoral immunity to infectious agent "Circulating body fluid" refers to blood, lymph, and hemolymph. Alexander Diehl Albert Goldfain An immunity to infectious agent that inheres in an organism in virtue of components of its circulating body fluid. The disposition is realized in a humoral immune response. Lindsay Cowell leukocyte-mediated immunity to infectious agent Albert Goldfain An immunity to infectious agent that inheres in an organism in virtue of its leukocytes. cell-mediated immunity to infectious agent Lindsay Cowell The disposition is realized in a leukocyte-mediated immune response. Alexander Diehl passive immunity to infectious agent The protective antibodies are typically introduced by injection, breast feeding, or by passing from the placenta to the fetus. Alexander Diehl An immunity to infectious agent that inheres in an organism in virtue of antibodies not produced by that organism. Lindsay Cowell Passive immunity results from a passive immunization. The disposition is realized in a neutralizing process carried out by the antibodies. Albert Goldfain antibiotic resistance Albert Goldfain Lindsay Cowell Alexander Diehl A resistance to drug that mitigates the damaging effects of an antibiotic. long-term non-progressor Alexander Diehl An organism experiencing a long-term non-progressing infectious disease course. Lindsay Cowell Albert Goldfain emerging pathogen Albert Goldfain Lindsay Cowell Alexander Diehl An infectious agent whose infection incidence is increasing following its first introduction into a new host Species. cytotoxin Alexander Diehl A molecular entity with a toxin disposition, the realization of which damages host cells. Albert Goldfain Lindsay Cowell collective pathogenic disposition Albert Goldfain Alexander Diehl The disposition is realized in processes that create a disorder. A collective disposition to initiate processes that result in a disorder. Lindsay Cowell infection Lindsay Cowell A part of an extended organism that itself has as part a population of one or more infectious agents and that is (1) clinically abnormal in virtue of the presence of this infectious agent population, or (2) has a disposition to bring clinical abnormality to immunocompetent organisms of the same Species as the host (the organism corresponding to the extended organism) through transmission of a member or offspring of a member of the infectious agent popuation. Albert Goldfain Alexander Diehl The organism corresponding to the extended organism is host to the infectious agents. By this definition, parts of the host can be considered part of the infection. genetic resistance to infectious agent The resistance of individuals to HIV invasion oonferred by particular CCR5 alleles is an example. Resistance against malaria conferred by the sickle cell gene is another. Alexander Diehl A resistance to infectious agent that inheres in an organism in virtue of a specific allele or combination of alleles in its genome. Lindsay Cowell Albert Goldfain collective resistance disposition Lindsay Cowell Albert Goldfain A collective disposition the realization of which mitigates the damaging effects of some entity on members of the collection. Alexander Diehl immunodeficient organism Alexander Diehl An organism that has an immunodeficiency. Lindsay Cowell Albert Goldfain immunocompromised organism chronic infectious disease course Lindsay Cowell Albert Goldfain Alexander Diehl An infectious disease course that unfolds over a long period of time. persistent infectious disease course immune population An organism population whose members have acquired immunity to an infectious agent. Lindsay Cowell Albert Goldfain Alexander Diehl transmission period A continuous temporal interval during which a transmission process occurs. Alexander Diehl Lindsay Cowell Albert Goldfain direct host exposure to infectious agent Bjoern Peters A process in which a potential host of an infectious agent comes into direct physical contact with the infectious agent. potential host of infectious agent Alexander Diehl Albert Goldfain An organism that has the capability to bear a host of infectious agent role. Lindsay Cowell infectious agent Albert Goldfain Alexander Diehl Lindsay Cowell An organism that has an infectious disposition. host exposure to environment containing infectious agent A process in which a potential host of an infectious agent is exposed to an environment in which the infectious agent is present and physical contact between the two can occur, but such contact is not planned. Bjoern Peters host living with infected household contact Alexander Diehl Bjoern Peters Lindsay Cowell Albert Goldfain A host exposure to environment with infectious agent where the environment is a household that also has an infected host Alan Ruttenberg 2010/05/20- Tentative definition. Needs review by Bjoern host living in endemic area Lindsay Cowell Albert Goldfain Alan Ruttenberg 2010/05/20- Tentative definition. Needs review by Bjoern Bjoern Peters Alexander Diehl A host exposure to environment with infectious agent where the environment is an area in which an infectious agent is endemic release of infectious human pathogen in laboratory Alexander Diehl A host exposure to environment with infectious agent where the exposure is accidental; the environment is a laboratory, and the infectious agent is infectious in humans. Alan Ruttenberg 2010/05/20- Tentative definition. Needs review by Bjoern Albert Goldfain Lindsay Cowell Bjoern Peters host coming into contact with vector of infectious agent Alan Ruttenberg 2010/05/20- Tentative definition. Needs review by Bjoern Albert Goldfain Lindsay Cowell Alexander Diehl Bjoern Peters A host exposure to environment with infectious agent where the environment contains an infectious agent vector. host exposure to substance that might have infectious agent Bjoern Peters Alexander Diehl A host exposure to environment with infectious agent where the environment contains a material entity that has been assessed to confer a risk of infection. Alan Ruttenberg 2010/05/20- Tentative definition. Needs review by Bjoern Albert Goldfain Lindsay Cowell process of establishing an infection Albert Goldfain Lindsay Cowell A process by which an infectious agent, established in a host, becomes part of an infection in the host. Alexander Diehl colonization of host An establishment in host process in which an organism establishes itself in a host. Lindsay Cowell Albert Goldfain Alexander Diehl Establishment of one organism in the extended organism of another (the host) involves at least one of (1) movement of the organism to a location within the host in which the organism can persist, or (2) adherence or attachment of the organism to part of the host. establishment of a clinically abnormal colony Lindsay Cowell Albert Goldfain A colonization of host process that results in a clinically abnormal colony. Alexander Diehl production A process in which an entity comes into being as a result of the process. Alexander Diehl Lindsay Cowell Albert Goldfain replication Albert Goldfain Lindsay Cowell A production process in which a participant creates a copy of itself. Alexander Diehl colonization of human anterior nares Alexander Diehl A colonization of human process in which the colonized site is the anterior nares. Albert Goldfain Lindsay Cowell immunosuppression Lindsay Cowell Albert Goldfain A process that attenuates an immune response. Alexander Diehl physiologic immunosuppression Alexander Diehl Albert Goldfain An immunosuppression which unfolds as part of the natural self-regulation of an immune response. Lindsay Cowell pathologic immunosuppression Albert Goldfain An immunosuppression process which arises as the result of a disorder. Lindsay Cowell Alexander Diehl Disorders that result in immunosuppression include those that result from infection, stress, malnutrition, and treatments such as chemotherapy or calcineurin inhibition. colony Lindsay Cowell Albert Goldfain Alexander Diehl An organism population persisting in a site it has colonized. infectious agent colony Albert Goldfain Alexander Diehl A colony whose members are infectious agents. Lindsay Cowell immunodeficiency DL needs immune system component (FMA?) and defective functioning (OGMS?) Lindsay Cowell Albert Goldfain A disorder of an immune system component that results in defective functioning of the immune system. Alexander Diehl immunocompetence The disposition inheres in a bearer in virtue of the fact that the bearer has all canonical immune system components and none are disordered. The disposition is realized in a successful immune response. A disposition that is the ability to mount a normal immune response. Alexander Diehl Lindsay Cowell Albert Goldfain immunosuppressive disposition Albert Goldfain Lindsay Cowell Alexander Diehl A disposition whose realization negatively regulates an immune response. acquired immunity to infectious agent Lindsay Cowell Albert Goldfain The disposition is realized in an immune response in which such antigen receptors participate. Alexander Diehl An immunity to infectious agent that inheres in an organism in virtue of antigen receptors encoded by somatically diversified genes in the organism's genome and expressed by cells that have undergone selection during a primary immune response in that organism. adaptive immunity to infectious agent immune memory disposition to form a non-parasitic colony Alexander Diehl Lindsay Cowell A disposition to colonize an organism and participate in mutualism or commensalism with that organism. Albert Goldfain communicability Lindsay Cowell Albert Goldfain The disposition is realized in a direct, horizontal transmission process between members of the same Species. Alexander Diehl An infectious disposition to be transmitted directly from one organism to another of the same Species by horizontal transmission. establishment of localization in host Albert Goldfain An establishment of localization process in which a material entity reaches a site in an organism in which it can survive, grow, multiply, or mature. Lindsay Cowell Alexander Diehl Requested addition of this term to the GO. An organism begins bearing a particular host role as soon as the extended organism contains the relevant material entity, regardless of that entity's location in the extended organism. An establishment process is any process by which the entity reaches a location in the extended organism in which it can persist and continue its lifecycle. For example, an organism is host to a virus as soon as any part of the extended organism is occupied by virus particles. During an establishment process, virus particles enter host cells of the relevant type, and viral DNA is integrated into host DNA. appearance of disorder Lindsay Cowell Albert Goldfain Alexander Diehl A process by which a disorder comes into existence. acute infection Albert Goldfain Alexander Diehl An infectious disorder that is the physical basis for an unfolding acute infectious disease course. Lindsay Cowell chronic infection Lindsay Cowell Albert Goldfain DL needs 'extended period of time' Alexander Diehl An infection that persists for an extended period of time. persistent infection host role A role borne by an organism in virtue of the fact that it's extended organism contains a material entity other than the organism. Alexander Diehl Lindsay Cowell Albert Goldfain hospital-acquired infection Lindsay Cowell DL needs 'hospital' (OGMS?) Alexander Diehl Albert Goldfain An infection resulting from a transmission process that unfolds in a hospital. nosocomial infection community-acquired infection DL needs 'health care facility' Alexander Diehl An infection resulting from a transmission process that did not unfold in a health care facility. Lindsay Cowell Albert Goldfain neurotoxin Lindsay Cowell Albert Goldfain A molecular entity with a toxin disposition, the realization of which damages or interferes with the function of nerve tissue. Alexander Diehl metatstatic infection Alexander Diehl DL needs 'another infection in a non-adjacent location' Lindsay Cowell Albert Goldfain An infection established as a result of spread from another infection in a non-adjacent location in the extended organism of the host. source of infection role Alexander Diehl The role is realized in a process that has as part a transmission process and a process by which the infectious agent or one of its offspring becomes part of a disorder in the host. A role borne by a material entity in virtue of the fact that it contains a site from which an infectious agent is transmitted. Albert Goldfain Lindsay Cowell sepsis Albert Goldfain A process that is a systemic inflammatory response to infection. Lindsay Cowell Alexander Diehl severe sepsis Lindsay Cowell A sepsis that results in organ dysfunction, hypotension, or hypofusion of at least one organ. Albert Goldfain Alexander Diehl nursing-home acquired Albert Goldfain Alexander Diehl DL needs nursing home (OGMS?) Lindsay Cowell An infection resulting from a transmission process that unfolds in a nursing home. infectious human pathogen Lindsay Cowell Albert Goldfain Alexander Diehl An infectious agent with a capability to infect human hosts. acquired immunodeficiency Albert Goldfain Alexander Diehl An immunodeficiency that is not caused by a genetic predisposition. Lindsay Cowell Causes of acquired immunodeficiences include infection and drug treatments (e.g. chemotherapy). simple infection Alexander Diehl An infection comprised of infectious organisms all of the same Species. needs 'species' Lindsay Cowell Albert Goldfain re-emerging pathogen Lindsay Cowell Albert Goldfain Alexander Diehl An infectious agent whose infection incidence is increasing in a host population as a result of changes in the biology of the host or pathogen, or changes in their interactions. pregnancy-induced immunosuppression Alexander Diehl Lindsay Cowell Albert Goldfain An immunosuppression induced by progesterone and other factors upregulated in pregnant women. candidiasis DL needs NCBI taxonomy term. An infection that has as part organisms of the Genus Candida. Lindsay Cowell Albert Goldfain Alexander Diehl trichomoniasis An infection that has as part organisms of the Species Trichomonas vaginalis. DL needs NCBI taxonomy terms. Alexander Diehl Albert Goldfain Lindsay Cowell leptospirosis Albert Goldfain Lindsay Cowell DL needs NCBI Taxonomy term. Alexander Diehl An infection that has as part organisms of the Genus Leptospira. Shigellosis Lindsay Cowell An infection located in the bowel and that has as part organisms of the Genus Shigella. DL needs NCBI taxonomy term. Albert Goldfain Alexander Diehl amebiasis Alexander Diehl Albert Goldfain Lindsay Cowell DL needs NCBI taxonomy term. An infection located in the colon and that has as part organisms of the Species Entamoeba histolytica colonization of human Lindsay Cowell A colonization of host process in which the host is of Species Homo sapiens. Alexander Diehl Albert Goldfain primary immunodeficiency Alex Diehl Albert Goldfain Lindsay Cowell congenital immunodeficiency An immunodeficiency that exists in an organism because of a genetic predisposition. colonization of human perineum A colonization of human process in which the colonized site is a perineum. Alex Diehl Albert Goldfain Lindsay Cowell reverse zoonosis An infectious disease that has as its physical basis an infectious disorder composed of infectious agents that have a reverse zoonotic disposition. Alex Diehl Lindsay Cowell Albert Goldfain opportunistic pathogen Albert Goldfain opportunist Alex Diehl Lindsay Cowell An infectious agent with an opportunistic infectious disposition. transmissibility disposition A disposition to undergo a transmission process. Lindsay Cowell Alex Diehl The disposition is realized in a transmission process. Albert Goldfain horizontal pathogen transmission process A pathogen transmission process in which a pathogen is transmitted from one host to another of the same Species, and the two hosts are not in a parent-child relationship. Lindsay Cowell process that results in death A process that results in death. Lindsay Cowell Alex Diehl host exposure to infectious agent A process in which a potential host of an infectious agent is exposed to an infectious agent. Bjoern Peters susceptible organism An organism that is not infected with an infectious agent and lacks protective immunity to the infectious agent. Alex Diehl Lindsay Cowell life-sustaining process Lindsay Cowell A process which is necessary for the survival of an organism. Alex Diehl negative regulation of life-sustaining process Alex Diehl Any process that stops, prevents, or reduces the frequency, rate or extent of a life-sustaining process. Lindsay Cowell source of infection Albert Goldfain A material entity bearing a source of infection role. Alex Diehl Lindsay Cowell transition to clinical abnormality A process by which a part of an organism or something contained in an organism becomes clinically abnormal. brucellosis Rock of Gibraltar fever a zoonosis that is caused by Brucella. Bang’s disease undulant fever YH, YL, ZX Mediterranean fever Malta fever brucellosis symptom YH, YL, ZX a symptom that is observed by a brucellosis patient. human brucellosis symptom Malta fever a brucellosis symptom that appears in human. YH, YL, ZX cattle brucellosis symptom human brucellosis symptom YH, YL, ZX a brucellosis syptom shown in a cattle. a brucellosis symptom that observed in cattle. brucellosis cough YH, YL, ZX cough typically shown in a brucellosis patient. a brucellosis symptom that appears as cough. goat brucellosis symptom a brucellosis symptom shown in a goat. YH, YL, ZX a brucellosis symptom that appears in goat. swine brucellosis symptom a brucellosis symptom that appears in swine (pig). YH, YL, ZX undulant fever 'undulent fever' is often used as a synonym of human brucllosis. The exact use of this term requires some future discussion. YL, YH, ZX a human brucllosis symptom that is usually characterized by nonspecific febrile illness, including irregular and intermittent fever and chills and is observed in 90% of brucellosis cases. brucellosis arthritis arthritis typically shown in a brucellosis patient. YL, YH PMID: 18045560 brucellosis sweating sweating PMID: 18045560 YL, YH brucellosis hepatomegaly YL, YH hepatomegaly typically shown in a brucellosis patient. PMID: 18045560 brucellosis splenomegaly PMID: 18045560 splenomegaly typically shown in a brucellosis patient. YL, YH brucellosis anaemia YL, YH anaemia typically shown in a brucellosis patient. PMID: 18045560 brucellosis leucopenia PMID: 18045560 leucopenia typically shown in a brucellosis patient. YL, YH brucellosis leucocytosis YL, YH PMID: 18045560 leucocytosis typically shown in a brucellosis patient. brucellosis thrombocytopenia PMID: 18045560 YL, YH thrombocytopenia typically shown in a brucellosis patient. brucellosis thrombocytosis YL, YH thrombocytosis typically shown in a brucellosis patient. PMID: 18045560 brucellosis elevated CRP an elevated CRP typically shown in a brucellosis patient. PMID: 18045560 YL, YH brucellosis elevated ESR an elevated ESR typically shown in a brucellosis patient. PMID: 18045560 YL, YH brucellosis positive RF PMID: 18045560 YL, YH positive RF typically shown in a brucellosis patient. brucellosis arthralgia PMID: 18045560 arthralgia typically shown in a brucellosis patient. YL, YH brucellosis diurnal variation fever process YL, YH Fever is the most common(92.8% of adults, 87.5% of children) feature of brucellosis. There are no characteristic patterns which differentiate fever due to brucellosis from other febrile illnesses. The temperature usually shows diurnal variations, being high in the afternoon and evening and returning to normal in morning. This diurnal variation is of clinical importance as the treating clinician may find the temperature to be normal if the patient is seen in a morning clinic. The fever tends to subside if the patient rests in bed, and rises again following physical exercise. The temperature may be of a low grade and the patient may be unaware of its presence, and it can only be detected during hospitalization and regular measurements. The temperature usually ranges from 37.5-40C or higher. P76 Madkour, M. Monir, Brucellosis, 1989, ISBN 0-7236-9041-1 PMID: 18045560 brucellosis chill PMID: 18045560 YL, YH chill typically shown in a brucellosis patient. brucellosis anorexia YL, YH anorexia typically shown in a brucellosis patient. PMID: 18045560 brucellosis malaise PMID: 18045560 YL, YH malaise typically shown in a brucellosis patient. brucellosis asthenia YL, YH asthenia typically shown in a brucellosis patient. PMID: 18045560 brucellosis weight loss PMID: 18045560 weight loss typically shown in a brucellosis patient. YL, YH human brucellosis YL, YH brucellosis that is beared by a human. swine brucellosis brucellosis that is beared by a swine (pig). YL, YH horse brucellosis YL, YH brucellosis that is beared by a horse. cattle brucellosis brucellosis that is beared by a cattle. YL, YH sheep brucellosis brucellosis that is beared by a sheep. YL, YH Brucella virulence factor YH, YL, ZX virulence factor that bears Brucella virulence factor dispositon brucellosis test PCR primer PCR assay for detecting B. abortus gene BCSP31 YL, YH PubMed: 11574607 A PCR test for brucellosis that is a single step PCR for the detection of a 223 bp region encoding Brucella abortus protein BCSP31 in peripheral blood samples is used in the diagnosis of human brucellosis(Casanas et al., 2001, Quiepo-Ortuno et al., 1997). The same PCR test can also be used for samples from focal lesions. B. abortus specific primer for AMOS and updated AMOS sub acute disease course YL an acute disease course temproally lasts up to a week. submit to OGMS later B. abortus specific forward primer for AMOS and updated AMOS Sequence: GACGAACGGAATTTTTCCAATCCC B. abortus specific reverse primer for AMOS and updated AMOS Sequence: TGCCGATCACTTAAGGGCCTTCAT B. melitensis specific primer for AMOS and updated AMOS B. melitensis specific forward primer for AMOS and updated AMOS Sequence: AAATCGCGTCCTTGCTGGTCTGA B. melitensis specific reverse primer for AMOS and updated AMOS Sequence: TGCCGATCACTTAAGGGCCTTCAT B. ovis specific primer for AMOS and updated AMOS B. ovis specific forward primer for AMOS and updated AMOS B. ovis specific reverse primer for AMOS and updated AMOS B. suis specific primer for AMOS and updated AMOS B. suis specific forward primer for AMOS and updated AMOS B. suis specific reverse primer for AMOS and updated AMOS brucellosis diagnosis by PCR test YL brucellosis diagnosis made by using PCR test method YH,YL RB51/2308 primer for updated AMOS RB51/2308 forward primer for updated AMOS RB51/2308 reverse primer for updated AMOS eri primer for updated AMOS eri forward primer for updated AMOS eri reverse primer for updated AMOS primer for single step PCR forward primer for single step PCR reverse primer for single step PCR wboA gene primer for B. abortus vaccine RB51 wboA gene forward primer for B. abortus vaccine RB51 wboA gene reverse primer for B. abortus vaccine RB51 wboA gene with part of IS711 primer for B.abortus vaccine RB51 wboA gene with part of IS711 forward primer for B.abortus vaccine RB51 wboA gene with part of IS711 reverse primer for B.abortus vaccine RB51 omp-2 primer omp-2 forward primer omp-2 reverse primer patient derived specimen YL specimen that derives from a patient amplification product of brucellosis PCR assay YL a PCR product that is the output of the PCR assay used in diagnosing brucellosis brucellosis diagnosis by microscopy brucellosis diagnosis made base on the observation from microscopy The BACTEC 9240 continuous monitoring system uses broth to culture bacteria from human blood samples; after culturing the samples are stained with Gram's stain and observed using light microscopy; suspicious cultures are tested with further biochemical tests. YL,YH brucellosis diagnosis by immunoassay test YH brucellosis diagnosis made base on the positive result of immunoassay test brucellosis diagnosis by Coombs test brucellosis diagnosis made base on the positive result of Coombs test YL,YH brucellosis diagnosis by complement fixation test brucellosis diagnosis made base on the positive result of complement fixation test YL,YH brucellosis diagnosis by competitive ELISA YL,YH brucellosis diagnosis made base on the positive result of competitive ELISA brucellosis diagnosis by radial immunodiffusion test YL,YH brucellosis diagnosis made base on the radia immunodiffusion test brucellosis diagnosis by counter immunoelectrophoresis YL,YH brucellosis diagnosis made base on the counter immunoelectrophoresis brucellosis diagnosis by Milk Ring Test brucellosis diagnosis made base on the positive result of Milk Ring Test YL,YH brucellosis diagnosis by Brucellacapt brucellosis diagnosis made base on the positive result of Brucellacapt YH,YL brucellosis diagnosis by Serum Agglutination Test (SAT) brucellosis diagnosis made base on the positive result of Serum Agglutination Test YL,YH brucellosis diagnosis by Rose Bengal Test (RB) brucellosis diagnosis made base on the positive result of Rose Bengal Test YL,YH brucellosis diagnosis by 2-Mercapto-ethanol Test (2-ME) YH,YL brucellosis diagnosis made base on the positive result of 2-Mercapto-ethanol Test brucellosis diagnosis by Skin Delayed-Type Hypersensitivity Test (SDTH) brucellosis diagnosis made base on the positive result of Skin Delayed-Type Hypersensitivity Test YL,YH brucellosis diagnosis by Dipstick Assay brucellosis diagnosis made base on the positive result of Dipstick Assay YL,YH brucellosis diagnosis using PCR assay for detecting Brucella omp-2 brucellosis diagnosis made based on the PCR assay that is detecting the Brucella omp-2 gene. All the sequence data of primers and PCR product are parts of the genome sequence data from either B. abortus or B. melitensis, suggesting that the test can detect both of these species {Leal-Klevezas, 1995}. YL Brucella life course YL the life course that has Brucella as participant clinical manifestation of brucellosis YL, YH a clinical manifestation of brucellosis. preclinical manifestation of brucellosis YL, YH a preclinical manifestation of brucellosis. Brucella infected organism brucellosis patient specimen Brucella infected homo sapiens Brucella infected human Brucella infected cow Brucella infected cattle Brucella infected swine brucella infected horse Brucella infected sheep coombs test for human brucellosis YL, YH PubMed: 11060059 PubMed: 9684294 The Coombs Test is a diagonostic test using manufactured antigen and antiglobulins to detect the presence of specific antibodies. It is used very commonly in the detection of human brucellosis, but due to expense and time factors is used less often to detect animal brucellosis. complement fixation test for cattle brucellosis PubMed: 9684294 YL, YH The complement fixation test (CFT), used to diagnose brucellosis in cattle, detects specific IgM and IgG1 antibodies. competitive ELISA for brucellosis Competitive ELISA detects serum antibody and is able to distinguish between vaccine and infection derived antibodies. ELISA is used for detection of brucellosis in humans, cattle, sheep and goats. PubMed: 10488186 PubMed: 8051240 YL, YH radial immunodiffusion test for sheep brucellosis PubMed: 8051240 YL, YH A radial immunodiffusion (RID) test uses manufactured Brucella antigens in a gelling agent with wells for goat serum. Sera positive for antibodies to Brucella will diffuse into the gelling agent and cause a visible color change. RID counter immunoelectrophoresis for sheep brucellosis Counter immunoelectrophoresis (CIEP) is used to detect brucellosis in goats. Manufactured antigen binds with antibodies present in sera and the combination is electrophoresed to analyze antibody titers. PubMed: 8051240 YL, YH brucellosis sign YH, YL, ZX a symptom that is observed by a clinician. sterility a symptom that is observed by a brucellosis patient. YH, YL, ZX brucellosis disposition Brucellosis disposition that is the disposition to be transmitted from an infected, non-human host to a human host. YL brucellosis diagnosis YH, YL, ZX a diagnosis for brucellosis PCR assay for detecting B. abortus vaccine RB51 a brucellosis diagnosis that detects the presence of B. abortus vaccine RB51. YH, YL, ZX Brucella abortus vaccine strain RB51 is a natural stable attenuated rough mutant derived from the virulent strain 2308. The genetic mutations that are responsible for the roughness and the attenuation of strain RB51 have not been identified until now. It was demonstrated that the wboA gene encoding a glycosyltransferase, an enzyme essential for the synthesis of O antigen, is disrupted by an IS711 element in B. abortus vaccine strain RB51. The PCR assay developed here can distinguish strain RB51 from all other Brucella species and strains tested. PCR assay for detecting B. abortus 16S rRNA YH, YL, ZX a PCR assay for brucellosis that is designed to detect Brucella 16S rRNA. PubMed: 7538508 This is a PCR assay with primers derived from the 16S rRNA sequence of Brucella abortus. The pair of primers chosen amplified a 905bp fragment. As little as 80 fg of Brucella DNA was detected by this method. DNAs from all of the representative strains of the species and biovars of Brucella and from 23 different Brucella isolates were analyzed and yielded exclusively the 905-bp fragment. No amplification was detected with DNAs from 10 strains phylogenetically related to Brucella spp., 5 gram-negative bacteria showing serological cross-reactions with Brucella spp., and 36 different clinical isolates of non-Brucella species. Only Ochrobactrum anthropi biotype D yielded a PCR product of 905 bp, suggesting a closer relationship between Brucella spp. and O. anthropi biotype D. The specificity and high sensitivity of the PCR assay may provide a valuable tool for the diagnosis of brucellosis. PCR to amplify 193bp region located in Brucella omp-2 gene A versatile method for the extraction of Brucella DNA and PCR are presented as reliable tools for the detection of Brucella spp. from body fluids of infected animals. Two oligonucleotides homologous to regions of the gene encoding for an outer membrane protein (OMP-2) were designed to detect the pathogen from milk and/or blood of infected goats, bovine, and human patients. The sensitivity of our test and its ability to detect the pathogen in samples from the field reveal a promising advance in the diagnosis of brucellosis in animals and humans. PubMed: 8586678 YH, YL, ZX a PCR assay that has an objective of amplying the 193 bp's region located in Brucella omp-2 gene. AMOS YH, YL, ZX PMID: 7852552 Several PCR assays which identify the genus Brucella but do not discriminate among species have been reported. We describe a PCR assay that comprises five oligonucleotide primers which can identify selected biovars of four species of Brucella. Individual biovars within a species are not differentiated. The assay can identify three biovars (1, 2, and 4) of B. abortus, all three biovars of B. melitensis, biovar 1 of B. suis, and all B. ovis biovars. These biovars include all of the Brucella species typically isolated from cattle in the United States, a goal of the present research. The assay exploits the polymorphism arising from species-specific localization of the genetic element IS711 in the Brucella chromosome. Identity is determined by the size(s) of the product(s) amplified from primers hybridizing at various distances from the element. The performance of the assay with U.S. field isolates was highly effective. When 107 field isolates were screened by the described method, there was 100% agreement with the identifications made by conventional methods. Six closely related bacteria (Agrobacterium radiobacter, Agrobacterium rhizogenes, Ochrobactrum anthropi, Rhizobium leguminosarum, Rhizobium meliloti, and Rhodospirillum rubrum) and two control bacteria (Bordetella bronchiseptica and Escherichia coli) tested negative by the assay. a PCR test for brucellosis that is called AMOS. PubMed: 7852552 updated AMOS PubMed: 7650203 a PCR test for brucellosis that is composed of updated AMOS. YH, YL, ZX PMID: 7650203 Distinguishing vaccine strains from strains that cause infections among vaccinated herds in the field is essential. To accomplish this, the PCR-based, species-specific AMOS assay (B. J. Bricker and S. M. Halling, J. Clin. Microbiol. 32:26602666, 1994) was updated to identify Brucella abortus vaccine strains S19 and RB51. Three new oligonucleotide primers were added to the five-primer multiplex Brucella AMOS PCR assay. Identification is based on the number and sizes of six products amplified by PCR. brucellosis treatment YH, YL, ZX a treatment for brucellosis. a treatment that has an objective to reduce the sign and symptom in brucellosis WHO recommended brucellosis treatment KEY POINTS ON TREATMENT OF BRUCELLOSIS IN HUMANS The essential element in the treatment of all forms of human brucellosis is the administration of effective antibiotics for an adequate length of time. Treatment of uncomplicated cases in adults and children eight years of age and older: doxycycline 100 mg twice a day for six weeks + streptomycin 1 g daily for two to three weeks. OR Doxycycline 100 mg twice a day for six weeks + rifampicin 600-900 mg daily for six weeks. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p41) YH, YL, ZX a brucellosis treatment that was recommended by WHO. rifampin Rifampicin is active in vitro against Brucella species, is remarkably lipid soluble, and it accumulates within eukaryotic cells. In order to provide a completely oral regimen with which to treat brucellosis, the combination of doxycycline (200 mg/day orally) plus rifampicin (60000 mg/day orally), with both drugs administered for six weeks, was recommended by the WHO Expert Committee in 1986. This regimen has generally been found to be of similar efficacy to doxycycline plus streptomycin for patients with uncomplicated brucellosis. Caution is advised when considering this regimen for patients with complications, such as spondylitis. An analysis of various treatment regimens concluded that overall the regimen of doxycycline plus streptomycin was likely to be the most effective. In addition, some data have been reported indicating that rifampicin might enhance the plasma clearance of doxycycline, thus yielding subtherapeutic levels a possible explanation of treatment failures with this regimen. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p37) YH.YL B.abortus RB 51 is resistant to rifampicin. doxycycline antibiotic that is doxycycline YL, YH YL Brucella protein ZX, YH, AL A protein synthesized by Brucella spp. host anti-Brucella process Brucella virulence factor disposition ZX, YH, AL A disposition borne by a biological macromolecule produced by Brucella spp. that is the disposition to improve survival of the pathogen in a host, improve transmission of the pathogen to a host, or cause pathological processes in a host. genetic material form OBI's mail. Alan R. proposed this term, and we are waiting for the proval from the community. YL2011/02/16 Brucella protective antigen an antigen that is specifically targeted by the acquired immune response of the host and is able to induce protection in the host against infectious and non-infectious diseases. PMID: 20959289 YH, YL, ZX Brucella protective antigen role PMID: 20959289 YL, YH, ZX Protective antigen role is a role of protective antigen. Protective antigens are specifically targeted by the acquired immune response of the host and are able to induce protection in the host against infectious and non-infectious diseases. Milk Ring Test for Brucella in cow's milk MRT PubMed: 9684294 The milk ring test is a serological test for lacteal anti-Brucella IgM and IgA bound to milk fat globules in cow or goat milk. False Positive: False positives may occur with this test in colostrum, milk at the end of a lactation period, or cows suffering from a hormonal disorder or mastitis; however the specificity is reported to be 99%. False Negative: False negatives may occur with this test in milk with a low concentration of lacteal antibodies or lacking fat-clustering factors; the sensitivity is reported to be 56%. YL, YH PCR primer PCR forward primer PCR reverse primer B. abortus 16S rRNA PCR forward primer Sequence: TCGAGCGCCCGCAAGGGG B. abortus 16S rRNA PCR reverse primer Sequence: AACCATAGTGTCTCCACTAA brucellacapt for human brucellosis Brucellacapt is an immunocapture agglutination test for the serodiagnosis of human brucellosis. YL, YH PubMed: 11060059 PCR forward primer role YL, YH a primer role that is specifically for the PCR forward primer. PCR reverse primer role YL, YH a primer role that is specifically for the PCR reverse primer. Brucella ovis lipopolysaccharide YL YL,YH Brucella lipopolyasccharide that is part of Brucella ovis Brucella contaminated milk producing disposition a milk producing disposition that produces Brucella-contaminated milk. YL, YH Brucella abortus infection diagnosis by PCR test YL Brucella abortus infection diagnosis made by PCR test method YH,YL Brucella melitensis biovar 1 infection diagnosis by PCR test YL,YH diagnosis of brucella melitensis biovar 1 infection made by PCR test Brucella melitensis biovar 2 infection diagnosis by PCR test diagnosis of brucella melitensis biovar 2 infection made by PCR test YL,YH Brucella melitensis infection diagnosis by PCR test YH diagnosis of brucella melitensis infection made by PCR test Brucela melitensis biovar 3 infection diagnosis by PCR test diagnosis of brucella melitensis biovar 3 infection made by PCR test YL,YH Brucella abortus biovar 1 infection diagnosis by PCR test diagnosis of brucella abortus biovar1 infection made by PCR test YL,YH Brucella abortus biovar 2 infection diagnosis by PCR test YL,YH diagnosis of Brucella aborus biovar2 made by PCR test Brucella abortus biovar 3 infection diagnosis by PCR test diagnosis of Brucella abortus biovar3 infection made by PCR test YL,YH Brucella abortus biovar 4 infection diagnosis by PCR test YL,YH diagnosis of brucella abortus biovar 4 infection made by PCR test Brucella abortus biovar 5 infection diagnosis by PCR test diagnosis of brucella abortus biovar 5 infection made by PCR test YL,YH Brucella abortus biovar 6 infection diagnosis by PCR test YL,YH diagnosis of brucella abortus biovar 6 infection made by PCR test Brucella abortus biovar 7 infection diagnosis by PCR test diagnosis of brucella abortus biovar 7 infection made by PCR test YL,YH Brucella abortus biovar 9 infection diagnosis by PCR test diagnosis of brucella abortus biovar 9 infection made by PCR test Brucella suis infection diagnosis by PCR test diagnosis of brucella suis infection made by PCR test YL,YH Brucella suis biovar 1 infection diagnosis by PCR test YL,YH diagnosis of brucella suis biovar 1 infection made by PCR test Brucella suis biovar 2 infection diagnosis by PCR test diagnosis of brucella suis biovar 2 infection made by PCR test YL,YH Brucella suis biovar 3 infection diagnosis by PCR test diagnosis of brucella suis biovar 3 infection made by PCR test YL,YH Brucella suis biovar 4 infection diagnosis by PCR test YL,YH diagnosis of brucella suis biovar 4 infection made by PCR test Brucella suis biovar 5 infection diagnosis by PCR test diagnosis of brucella suis biovar 5 infection made by PCR test YL,YH PCR assay for brucellosis YL laboratory test for brucellosis that uses PCR method laboratory test for brucellosis YL laboratory test that is used for testing brucella infection Brucella infection test by culturing YL the process of testing brucella infection by culturing the specimen derived from patient. Immunoassay test for brucellosis YL laboratory test for testing brucella infection by using immuoassay letter string DNA Sequences from Below: A Nominalist Approach -Yu Lin & Peter Simons (http://sites.google.com/site/petermsimons/peter-s-files/DNASequencesfromBelow.pdf) We say W is a string of its elements E iff (Def.) there is a relation defined on the elements E which is connected, asymmetric, bi-directionally unique or non-splitting, and has exactly two free ends. Here we limit the element as "letter", which denotes the information entity of writing. YL DNA sequence data will be replaced by OBI term YL,YH,ZX genome YL A genome is a part of a organism that 1) is the total set of different DNA molecules of an organelle, cell or organism.2) consists DNA molecules. (The human genome consists of 25 different DNA molecules: the mitochondrial DNA molecule plus the 24 different chromosomal DNA molecules.) YL,YH Genome,Gene,Interval and Ontology by Yu Lin and Norihiro Sakamoto; published in 'Interdisciplinary Ontology', 2009 "http://cdb-riken.academia.edu/LinYu/Papers/142399/Genome_Gene_Interval_and_Ontology In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA.(http://en.wikipedia.org/wiki/Genome) DNA primer sequence data YL,YH,ZX DNA sequence data of primer that is used in PCR. serum agglutination test for human and bovine brucellosis PubMed: 9684294 YL, YH PubMed: 11060059 SAT The Serum agglutination test (SAT) is used commonly in the detection of both human and bovine Brucella specific antibodies. rose bengal test for bovine brucellosis PubMed: 8051240 PubMed: 9684294 RB test The RB test is a spot agglutination technique that uses dyed B. abortus antigen to detect serum antibodies of bovine brucellosis. YL, YH 2-Mercapto-ethanol Test for cattle brucellosis 2-ME 2ME PubMed: 9684294 The 2ME test is usually used in serial testing to distinguish between vaccinated and infected cattle. YL a immunoassay test for brucellosis that uses 2-Mercapto-ethanol differentiates between IgM and IgG antibodies and used to identify a recent immune response to an infectious agent. (http://medical-dictionary.thefreedictionary.com/2-mercaptoethanol+(2+ME)+test) skin delayed-type hypersensitivity test for brucellosis PubMed: 10952440 SDTH The SDTH test uses manufactured brucellin to elicit a skin hypersensitivity in livestock infected with acute, chronic, or latent brucellosis. YL, YH dipstick assay for acute human brucellosis A dipstick assay for rapid detection of Brucella specific immunoglobulin uses manufactured Brucella antigen on a nitrocellulose strip. When incubated for three hours with a serum sample, positive samples will form a distinct line, which can be graded from 1-4. PubMed: 10565959 YL, YH brucellosis patient derived blood specimen YL brucellosis patient specimen that is from blood temporal distribution S.Ali Veterinary epidemiology, Michael Thrusfield. Wiley-Blackwell, 2007. pp 144 Temporal distribution is the description of the occurence of the disease over time. The temporal changes and fluctuations in disease occurence can be classified into three major trends: Short term (typically epidemics), Cyclic (including seasonal which are regular periodic fluctuations in disease occurence), and Long term (Secular). tetracycline Tetracycline (500 mg every six hours orally) administered for at least six weeks has long been the standard treatment of human brucellosis. Doxycycline (a long acting tetracycline analogue) is now the preferred drug because it can be given once or twice daily, and is associated with fewer gastrointestinal side effects than tetracycline. Doxycycline is given in a dose of 100 mg every 12 hours orally and is administered for a period of six weeks. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p36) YH,YL intentional release YL a planned process that has an objective of releasing biological agent, usualy has bioterrorism agent as participant. Brucella intentional release Brucella can be used for bioterrorism. Intentional release is a process that intentionally release Brucella to the environment for bioterrorism purpose. Brucella organisms could be released in aerosol form, by accidental spills of culture suspensions or live vaccines, or in liquids such as dairy products or water. Brucellosis has fairly low fatality rate, but could be used as an incapacitating agent, as the disease tends to be chronic, requiring prolonged treatment. We need to model the following: # Emergency Contact: Local health departments and local law enforcement agencies should be contacted in the event of accidental or intentional release of Brucella species(Website 3). # Delivery Mechanism: Brucella organisms could be aerosolized and released at infectious doses. 10-500 organisms in aerosol form constitute an infectious dose. # Containment: Most commercial disinfectants are effective at killing or neutralizing Brucella organisms. Reference: http://www.phidias.us/phinfo/topicSearchResult.php?showall=1&pathogenID[]=3#section_biosafty YL YL,YH intentional release process that has an objective of release aerosolized Brucella. accidental release YL accidentally release an disease agent or biohazard agent that is not intended. Brucella accidental release YL Accidentally release process of brucella pasteurization A planned process of heating a liquid entity, to a specific temperature of a defined length of time span, and then cooling it immediately. It has an objective of prevent the microbial's growth in the liquid entity, which is a specific input of this planned process. Pasteurization is a process of heating a food, usually liquid, to a specific temperature for a definite length of time, and then cooling it immediately. This process slows microbial growth in food. (http://en.wikipedia.org/wiki/Pasteurization) YL pasteurization of dairy product YL pasteurization process has dairy product as input pasteurization of dairy product potentially containing Brucella YH YL dairy product pasteurization that has objective of preventing brcuella's growth, with an input of the dairy product that potentially contains Brucella. milk pasteurization YL pasteurization process has milk as input pasteurization of milk potentially containing Brucella YL milk pasteurization that has objective of preventing brcuella's growth, with an input of the milk that potentially contains Brucella. eradication of infectious disease YH Eradication is the reduction of an infectious disease's prevalence in the global host population to zero.[1] It is sometimes confused with elimination, which describes either the reduction of an infectious disease's prevalence in a regional population to zero, or the reduction of the global prevalence to a negligible amount. Further confusion arises from the use of the term eradication to refer to the total removal of a given pathogen from an individual (also known as clearance of an infection), particularly in the context of HIV and certain other viruses where such cures are sought. (http://en.wikipedia.org/wiki/Eradication_of_infectious_diseases) a process that has an objective to reduce the epidemic of infectious disease brucellosis eradication YH process of eradication that has a objective specification of reduce brucellosis epidemic eradication of non-human brucellosis * Description: Eradication of domestic animals infected with brucellosis, * Efficacy: o Rate: 100% eradication leads to dramatic decreased chance of transmission of brucellosis to humans. o Duration: Duration of efficacy equals duration of effective eradication. * Contraindicator: No contraindicators known, * Complication: False positives and negatives complicate diagnosis of domestic animals and wild animal reservoirs may not be available for testing. Importation of infected animals would renew population prevalence, YH PubMed: 8562733 brucellosis eradication that has objective of reducing non-human brucellosis antibiotic brucellosis treatment YL brucellosis treatment that uses antibotic aminoglycoside Because the rate of relapse when tetracycline or doxycycline are given alone remains between 100%, most authorities recommend an amino-glycoside to be given in addition to the tetracyclines for the first two to three weeks of therapy. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p37) YH, YL streptomycin Streptomycin (1 g/day intramuscularly) administered for two to three weeks has long been the aminoglycoside of choice when used in combination with tetracycline or doxycycline. Although synergy between the two drugs is difficult to prove using routine in vitro assays, bacterial killing studies have shown that Brucella species undergo a more rapid rate of killing by the combination than by either drug alone. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p37) gentamicin YH,YL Gentamicin is more active in vitro against Brucella species than streptomycin and, when administered as a single daily dose, is associated with few adverse side-effects. Although gentamicin, in a dose of 5mg/kg/day intravenously or intramuscularly, administered for 7 to 10 days in combination with doxycycline administered for six weeks, yielded good results in one study, experience with this regimen is too limited to justify its use over doxycycline plus streptomycin. Unfortunately, no direct study comparing the results of doxycycline plus streptomycin versus doxycycline plus gentamicin has yet been published. Until additional experience is gained using gentamicin in place of streptomycin, the optimal dose and duration of therapy remain unknown. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p37) WHO standard treatment for human brucellosis specification fluoroquinolone YH,YL Fluoroquinolone antibiotics have greater activity in vitro against Brucella species than the parent drug nalidixic acid. In addition, they are well absorbed after oral administration, and they achieve high concentrations within phagocytic cells. Although the minimum bactericidal concentration of quinolones is reported to be approximately four times the minimum inhibitory concentration, a lack of bactericidal activity was found at pH levels comparable to those found within cells. In addition, when quinolones were used as monotherapy in experimental animals and humans infected with Brucella, the rates of relapse were unacceptably high. Therefore, quinolones should always be used in combination with other drugs, such as doxycycline or rifampicin. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p38) trimethoprim/sulfamethoxazole TMP/SMZ in a fixed ratio of 1:5 (80 mg TMP/400 mg SMZ) is more active in vitro against Brucella species than either drug alone. Although initial studies with TMP/ SMZ reported good results, prospective, controlled, comparative trials demonstrated that the drug was associated with an unacceptably high rate of relapse. Consequently, TMP/SMZ should always be used in combination with another agent, such as doxycycline, rifampicin or streptomycin. (http://www.who.int/csr/resources/publications/Brucellosis.pdf p38) YH, YL TMP/SMZ co-trimoxazole WHO standard treatment for human brucellosis in adults and children eight years of age and older Treatment of uncomplicated cases in adults and children eight years of age and older: doxycycline 100 mg twice a day for six weeks + streptomycin 1 g daily for two to three weeks. WHO standard treatment for non-humanl brucellosis YH,YL YL a WHO brucellosis treatment that is for non-human brucellosis WHO principal alternative therapy for human brucellosis WHO recommended human brucellosis treatment YL a WHO brucellosis treatment that is for human brucellosis WHO secondary alternative therapy for human brucellosis WHO recommended treatment of human brucellosis during pregnancy WHO recommended treatment of brucellosis in children less than eight years of age Brucella infected goat Brucella infection YL Almost all domestic species can be affected with brucellosis except cats which are resistant to Brucella infection. Ref: EPIDEMIOLOGY AND EPIZOOTOLOGY OF BRUCELLOSIS: A REVIEW pvj.com.pk/pdf-files/27_3/page%20145-151.pdf YH,YL an infection that has part Brucella Brucella abortus infection Brucella melitensis infection Brucella suis infection Brucella canis infection brucellosis disease course a disease course that is realized by burcella infection human brucellosis disease course YL the brucellosis disease course happened in a human pathogen virulence process A biological process that is essential for a pathogen to survive in a host and be virulent to the host (e.g., a host organism or host cell). microbial pathogenesis process YL. YH survived infectious agent in host an infectious agent that eventually survives and replicates inside a host YH, YL survived Brucella in host YH, YL a survived infectious agent in host where the infectious agent is Brucella. part of Brucella mutant Brucella process towards host infection YL, YH a biological process of Brucella that has effects upon the host organism or host cell. attenuated Brucella strain Brucella host DNA sequence genetic material YL the physical DNA sequence that is part of a chromosome WEB.. http://cdb-riken.academia.edu/LinYu/Papers/149054/DNA_Sequences_from_Below_A_Nominalist_Approach cattle brucellosis disease course bovine brucellosis disease course the brucellosis disease course happened in a cattle sheep brucellosis disease course YL the brucellosis disease course happened in a sheep swine brucellosis disease course YL the brucellosis disease course happened in a swine cattle brucellosis pathogen role a brucellosis pathogen role that is beared in cattle. YL, YH human brucellosis pathogen role YL, YH a brucellosis pathogen role that is beared in human. brucellosis human patient Brucella infected dog process of establishing Brucella infection in host a process of establishing infection when the pathogen is a Brucella bacterium. YL patient role YL, YH a role of being a patient. should be replaced by OBI term brucellosis patient role a patient role that is for brucellosis patient. YL, YH drinking function a function of drinking that is realized by a drinking process. YL, YH milk drinking function a drinking function that is for drinking milk. YL, YH milk producing disposition a disposition that produces milk. YL, YH Brucella-contaminated milk YL YL extended milk that has brucella as its part milk producing process The natural production process of a cow that has milk as the final result. YL B. abortus 16S rRNA PCR primer bacterial O-polysaccharide temporal distribution of Brucellosis S. Ali The description of the occurence of Brucellosis over time. Brucella lipopolysaccharide a bacterial lipopolsaccharide that is from Brucella. YH, YL Brucella LPS Brucella abortus lipopolysaccharide YL,YH YL brucella lipopolysaccharide that is part of Brucella abortus Brucella melitensis lipopolysaccharide Brucella lipopolysaccharide that is part of Brucella melitensis YL YL,YH Brucella suis lipopolysaccharide Brucella lipopolysaccharide that is part of Brucella suis Brucella O-polysaccharide Brucella O-chain Brucella abortus O-polysaccharide Brucella melitensis O-polysaccharide Brucella suis O-polysaccharide brucellosis pathogen role a pathogen role of being a brucellosis pathogen. YL, YH Brucella host role YL, YH An infectious angent host role borne by an organism in virtue of the fact that its extended organism contains Brucella. goat brucellosis pathogen role a brucellosis pathogen role that is beared in goat. YL, YH sheep brucellosis pathogen role a brucellosis pathogen role that is beared in sheep. YL, YH camel brucellosis pathogen role YL, YH a brucellosis pathogen role that is beared in camel. pig brucellosis pathogen role a brucellosis pathogen role that is beared in pig. YL, YH dog brucellosis pathogen role YL, YH a brucellosis pathogen role that is beared in dog. dog brucellosis brucellosis that is beared by a dog. YL, YH camel brucellosis YL, YH brucellosis that is beared by a camel. goat brucellosis YL, YH brucellosis that is beared by a goat. geographic region goat brucellosis disease course YL the brucellosis disease course happened in a goat sheep brucellosis symptom YL, YH a brucellosis symptom shown in a sheep. camel brucellosis symptom YL, YH a brucellosis system shown in camel. camel brucellosis disease course YL the brucellosis disease course happened in a camel dog brucellosis disease course YL the brucellosis disease course happened in a dog dog brucellosis symptom a brucellosis symptom shown in a dog. YL, YH infectious disease endemic geographical region infectious disease free geographical region infectious disease non-endemic geographical region brucellosis endemic geographical region Salwa Ali brucellosis free geographical region Salwa Ali brucellosis non-endemic geographical region Salwa Ali brucellosis pathological bodily process YL YL a pathological bodily process that happens in brucellosis aerosolized Brucella YL aerosolized Brucella is a subclass of Brucella? it is Brucella in another form. How shall we represent this? Brucella aerosolization YL the planned process that has out put of an aerosol -- a fine mist or spray containing minute particles of brucella eradication of human brucellosis S.A., YL YL brucellosis eradication that has objective of reducing human brucellosis brucellosis epidemic YL realization of brucellosis that become epidemic disinfection of aerosolized Brucella YL the process of controling aerosolized Brucella that has a output of reduced or eliminated aerosolized Brucella in the air. bleach disinfection of aerosolized Brucella YL disinfection process of aerosolized Brucella that has a input of bleach bleach bleach that is a disinfectant and bears disinfectant role YL YL,YH Bleach refers to a number of chemicals that remove color, whiten, or disinfect, often via oxidation.Many bleaches have strong bactericidal properties, and are used for disinfecting and sterilizing. (http://en.wikipedia.org/wiki/Bleach) human brucellosis epidemic YL brucellosis epdiemic that happened in human non-human brucellosis epidemic YL brucellosis epdiemic that happened in non-human organism Brucella contaminated milk producing process The milk production process that has Brucella contaiminated milk as the final result, which usually caused by a Brucella-infected cow. YL Brucella vaccine preparation vaccine preparation that has a objective of preventing brucella infection Brucella infection incidence YL , YH an infection incidence that occurs in brucellosis patients. Brucella infection incidence proportion YL, YH an infection incidence proportion that happens in Brucella infection. Brucella infection incidence rate an infection incidence rate that occurs for Brucella infection. YL, YH Brucella infection prevalence an infection prevalence that is for Brucella infection. YL, YH brucellosis endemicity YL, YH an infectious disease endemicity that is specifically for brucellosis. human brucellosis endemicity a brucellosis endemicity that is specifically for human brucellosis. YL, YH non-human brucellosis endemicity YL, YH a brucellosis endemicity that is specifically for non-human brucellosis. brucellosis hyper-endemicity an infectious disease hyper-endemicity that is specifically for brucellosis. YL, YH human brcuellosis hyper-endemicity YL, YH a brucellosis hyper-endomicity is that specifically for human brucellosis. non-human brucellosis hyper-endemicity a brucellosis hyper-endomicity is that specifically for non-human brucellosis. YL, YH brucellosis incidence an infectious disease incidencea that is specifically for brucellosis. YL, YH human brucellosis incidence a brucellosis incidencea that is specifically for human brucellosis. YL, YH non-human brucellosis incidence a brucellosis incidencea that is specifically for non-human brucellosis. YL, YH brucellosis incidence proportion YL, YH an infectious disease incidence proportion that is specifically for brucellosis. human brucellosis incidence proportion YL, YH a brucellosis incidence proportion that is specifically for human brucellosis. non-human brucellosis incidence proportion YL, YH a brucellosis incidence proportion that is specifically for non-human brucellosis. brucellosis endemic rate YL, YH an infectious disease endemic rate that is specifically for brucellosis. human brucellosis endemic rate a brucellosis endemic rate that is specifically for human brucellosis. YL, YH non-human brucellosis endemic rate a brucellosis endemic rate that is specifically for non-human brucellosis. YL, YH brucellosis mortality rate an infectiuos disease mortality rate that is specfically for brucellosis. YL, YH brucellosis lifetime prevalence YL, YH an infectious disease lifetime prevalence that is specifically for brucellosis. brucellosis endemic level an infectious disease endemic level that is specfically for brucellosis. YL, YH brucellosis sporadicity YL, YH an infectious disease sporadicity that is specfically for brucellosis. brucellosis control program the process of controlling brucellosis that inteded to prevent the occurence of brucellosis YL WHO standard doxycycline treatement for human brucellosis YL human brucellosis treatment that is a standard in WHO, and uses docycycline as input,and is a part of WHO standard treatment for human brucellosis in adults and children eight years of age and older WHO standard streptomycin treatment for human brucellosis YL human brucellosis treatment that is a standard in WHO, and uses streptomycin as input, and it is a part of WHO standard treatment for human brucellosis in adults and children eight years of age and older objective of amplyfing a 193 region located in gene omp-2 PCR product of PCR assay for detecting Brucella omp-2 laboratory finding of Brucella omp-2 detection infectious disease endemic site YL a site that is infectious disease endemic submit to IDO-core brucellosis endemic site SA YL an infectious disease endemic site that is specific for brucellosis infectious disease free site SA YL a site that is considered as infectious disease free submit to IDO brucellosis free site SA YL an infectious disease free site that is specific for brucellosis infectious disease non-endemic site SA YL a site that is considered infectious disease non-endemic brucellosis non-endemic site SA YL an infectious disease non-endemic site that is specific for brucellosis. In these countries, the disease in humans has been controlled through the implementation of eradication programs, however cases do still occur and thus they cannot be considered completely free of the disease. protein coding gene a DNA sequence that codes for protein YL YL Brucella protein coding gene protein coding gene that is part of Brucella YL YL chromosome of Brucella spp. YL A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. (http://en.wikipedia.org/wiki/Chromosome) a genetic material that is an organized structure of DNA and protein found in Brucella cells. symbol of gene YL,YH,ZX a symbol that represents a gene symbol of protein YL,YH,ZX a symbol that represent protein amino acid sequence data will replaced by a OBI term Brucella protein amino acid sequence data amino acid sequence data that is about Brucella protein's primary structure. YL Brucella melitensis strain M5 probably equal to 16M real-time PCR for detecting B. abortus A number of different approaches can be used to generate the fluorescence signal. Three approachesSYBR Green I (a double-stranded DNA intercalating dye), 5-exonuclease (enzymatically released fluors), and hybridization probes (fluorescence resonance energy transfer)were evaluated for use in a real-time PCR assay to detect Brucella abortus. The three assays utilized the same amplification primers to produce an identical amplicon. This amplicon spans a region of the B. abortus genome that includes portions of the alkB gene and the IS711 insertion element. All three assays were of comparable sensitivity, providing a linear assay over 7 orders of magnitude (from 7.5 ng down to 7.5 fg). However, the greatest specificity was achieved with the hybridization probe assay(Newby et al., 2003). YL PCR assay for detecting Brucella omp-2 PubMed: 8586678 This is a versatile method for the extraction of Brucella DNA and PCR are presented as reliable tools for the detection of Brucella spp. from body fluids of infected animals. Two oligonucleotides homologous to regions of the gene encoding for an outer membrane protein (OMP-2) were designed to detect the pathogen from milk and/or blood of infected goats, bovine, and human patients. The sensitivity of our test and its ability to detect the pathogen in samples from the field reveal a promising advance in the diagnosis of brucellosis in animals and humans. a PCR test for brucellosis that is designed to detect Brucella omp2 gene. YH, YL, ZX geographic distribution "Geography of Disease." Encyclopedia of Public Health. Ed. Lester Breslow. Gale Cengage, 2002. eNotes.com. 2006. 12 Sep, 2011 <http://www.enotes.com/public-health-encyclopedia/ geography-disease> The study of disease distribution, or the geography of disease, reveals real differences in disease distribution among nations and in regions within nations. It is a simple way to draw attention to the disease risks associated with particular environments. disease reemerging Salwa Ali Re-emerging infectious diseases are diseases that once were major health problems globally or in a particular country, and then declined dramatically, but are again becoming health problems for a significant proportion of the population. chromosome 1 of Brucella melitensis 16M the chromosome 1 that found in Brucella melitensis 16M's cell Brucella infected skin animal dealer role a role of being an animal dealer YL, YH laboratory worker role YL, YH a role of being a lab worker research worker role a role of being a research worker. YL, YH veterinarian role a role of being a veterinarian. YL, YH abattoir worker role YL, YH a role of being an abattoir worker. butcher role YL, YH a role of being a butcher dog owner role a role of being a dog owner YL, YH dog handler role YL, YH a role of being a dog handler occupational disease An occupational disease is any chronic ailment that occurs as a result of work or occupational activity. YL, YH reemerging infectious disease Salwa Ali Re-emerging infectious diseases are diseases that once were major health problems globally or in a particular country, and then declined dramatically, but are again becoming health problems for a significant proportion of the population either due to upward trends in incidence or prevalence or because they show novel outbreak ranges (geographical or host). endemic disease a disease that is endemic. YL, YH non-endemic disease YL, YH a disease that is not endemic. brucellosis outbreak SA, YL in epidemiology, the occurrence of infection with a particular disease in a small, localized group, such as the population of a village. The term is sometimes used more broadly to refer to an epidemic or a pandemic. (http://medical-dictionary.thefreedictionary.com/outbreak) the occurence of brucellosis disease cluster YL, YH A disease cluster refers to a grouping of diseases that are related temporally and in proximity. Brucells infected aerosol PCR product sequence data The DNA sequence data of a PCR product YL disease cluster (1) Two or more cases of a relatively uncommon event or disease related in time and/or place perceived to be greater than expected by chance (2) An unusual aggregation, real or perceived, of health events that are grouped together in time and space, which is reported to a public health department (http://medical-dictionary.thefreedictionary.com/Disease+Cluster) SA animal husbandary SA YL a process of breeding and raising livestock. contact transmission process SA YL a transmission process of which the disease agent is transferred directly by biting, sucking, chewing or indirectly by inhalation of droplets, drinking of contaminated water, traveling in contaminated vehicles. food-borne transmission process SA YL the disease transmission process of which the disease agent is spread by consuming contaminated food or drink. Brucella entry into macrophage YL The process in which brucella enters a macrophage. YL air-borne transmission process SA YL spread of infection by droplet nuclei or dust through the air. Brucella intracellular replication in macrophage The replication of Brucella within macrophage. YL YL Brucella intracellular survival in macrophage YL YL the biological processof Brcuella's survival inside the macrophage cell that is part of the process of establishing Brucella infection establishment of Brucella intracellular localization YL the establishment of Brucella localization in host cell. establishment of Brucella macrophage localization YL YL the process of Brucella to establish its localization into macrophage cell B.abortus genome sequence data YL the DNA sequence data that is about the primary structure of B.abortus genome. sequence data of 139bp's region located in Brucella omp-2 gene a DNA sequence data that is about a 139bp's region located in Brucella omp-2 gene YL Burcella omp-2 gene sequence data YL DNA sequence data that is about Brucella omp-2 gene. continuous treatment duration YH, YL a temporal interval for a continuous treatment normal temperature a human body temperature that is considered normal. Most people think of a "normal" body temperature as an oral temperature of 98.6°F (37°C). This is an average of normal body temperatures. Your temperature may actually be 1°F (0.6°C) or more above or below 98.6°F (37°C). Also, your normal body temperature changes by as much as 1°F (0.6°C) throughout the day, depending on how active you are and the time of day. Body temperature is very sensitive to hormone levels and may be higher or lower when a woman is ovulating or having her menstrual period. (http://firstaid.webmd.com/body-temperature) YL elevated temperature a sign that shows elevated temperature. YL, YH body temperature staying normal YL the bodily process when body temperature measures as a normal temperature. body temperature elevation YL YL,YH the process of body temperature's going up. mornings during the course of disease YL mornings (from sun rise to 12pm) within the time span of diseae course afternoons during the course of disease YL all the afternoons (from 12pm to sunset time) within the time span of disease course livestock YL S.A. Livestock refers to one or more domesticated animals raised in an agricultural setting to produce commodities such as food, fiber and labor. The term "livestock" as used in this article does not include poultry or farmed fish; however the inclusion of these, especially poultry, within the meaning of "livestock" is common. (http://en.wikipedia.org/wiki/Livestock) domestic animal that bears a food production role. dairy products a material entity that is made from milk, and it is an output of a dariy factory's dairy production facility. YL S.A. delivery of Brucella infected livestock S.A. YL the process of moving Brucella infected livestock from one site to another site. abortion of Brucella infected livestock S.A. YL abortion process happens in a Brucella infectied livestock international travel S.A. a process of travel from one country to another country importation of dairy products S.A. YL the process of importing dariy products from abroad country Brucella infected meat S.A. extended meat that has brucella as its part Brucella infected liver S.A. extended liver that has brucella as its part. Brucella infected bone marrow S.A. extended bone marrow that has brucella as part. farmer role a role of being a farmer S.A. dairy worker role a role of being a dairy worker S.A. herdsman role a role of being a herdsman S.A. cattle rancher role S.A. a role of being a cattle rancher shepherd role a role of being a shepherd. S.A., YH Brucella infected products of conception country Since the political border is changing historically. A country specified the year is its instance. For example, People's Republic of China in 1950. YL, SA. a site that has a political border desrcibed by a geographical boundary, including all the entities ocuppies within this geographical boundary, such as people, building, river, mines, and so on. quarantine restriction of movement of individuals who have been exposed to infectious or communicable disease in order to prevent its spread (From Dorland, 28th ed & Black's Veterinary Dictionary, 17th ed). Salwa Ali S.A. Channel Islands S.A. Declared Brucellosis free in 1935. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Norway S.A. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Declared Brucellosis free in 1952. Sweden Declared Brucellosis free in 1957. S.A. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour screening Salwa Ali The evaluation of an asymptomatic person in a population, or examination of a large sample of animals in a population, to detect an unsuspected disease process not known to exist at the time of evaluation. Finland Declared Brucellosis free in 1960. S.A. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Denmark S.A. Declared Brucellosis free in 1962. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Switzerland S.A. Declared Brucellosis free in 1963. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour biosurveillance Monitoring of information sources of potential value in detecting an emerging epidemic, whether naturally occurring or the result of bioterrorism. Salwa Ali Rumania Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Declared Brucellosis free in 1969. S.A. United Kingdom Scotland was declared Brucellosis free in 1980, while England and Wales were declared free in 1981. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour S.A. Netherlands Declared Brucelllosis free in 1985. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour S.A. brucellosis surveillance Greece Austria Salwa Ali Austria was declared Brucellosis free in 1985. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Luxembourg Declared Brucellosis free in 1985. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour S.A. Cyprus S.A. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Declared Brucellosis free in 1985. disease surveillance system Salwa Ali Reference: Strengthening National Public Health Preparedness and Response to Chemical, Biological, and Radiological Agent Threats. Edited by C.E. Cummings and E. Stikova. IOS Press, 2007. P.25. A surveillance system is an information loop or cycle that involves health care proviers, public health agencies, and the public. A well functioning disease surveillance system includes case detection and registration, case confirmation, data reporting, data analysis, outbreak investigation, response and preparedness activities, feedback, and communication. Falkland Islands S.A. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour Declred Brucellosis free in 1994. Iceland Iceland has always been Brucellosis free. S.A. Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour US Virgin Islands Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour S.A. US Virgin Islands have always been Brucellosis free. USA S.A. Australia S.A. Canada S.A. France S.A. Mexico S.A. brucellosis health education Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. Salwa Ali Peru S.A. Argentina S.A. Spain S.A. Italy S.A. Portugal S.A. DNA extracted from brucellosis patient derived specimen Albania S.A. Republic of Macedonia S.A. Algeria S.A. Syria S.A. Turkey S.A. Iran S.A. Iraq S.A. Saudi Arabia S.A. Oman S.A. Kuwait S.A. Lebanon S.A. Kyrgyzstan S.A. Tajikistan S.A. Kazakhstan S.A. Armenia S.A. Turkmenistan S.A. Georgia S.A. Uzbekistan China S.A. India S.A. Mongolia S.A. Tibet S.A. smooth Brucella strain the smooth Brucella strain is Brucella that has a smooth lipopolysaccharide as its part. (smooth lipopolysaccharide has surface expression of the O polysaccharide ) YL Brucella infection test by blood culturing S.A. YL brucella infection test by culturing the blood dervied from patient. Brucella infection test by milk culturing S.A. YL brucella infection test culturing milk derived from infected non-human organism B.abortus genome YL YL. a genome that is part of Brucella abortus biohazard containment Provision of physical and biological barriers to the dissemination of potentially hazardous biologically active agents (bacteria, viruses, recombinant DNA, etc.). Physical containment involves the use of special equipment, facilities, and procedures to prevent the escape of the agent. Biological containment includes use of immune personnel and the selection of agents and hosts that will minimize the risk should the agent escape the containment facility. S.A. rough Brucella strain YL the rough Brucella strain is Brucella that has a rough lipopolysaccharide as its part. (rough lipopolysaccharide is lack of surface expression or reduced surface expression of the O polysaccharide ) brucellosis diagnostic process YL the diagnostic process of making diagnosis of brucellosis Health Surveillance TeutschSM & Churchill RE (eds). Principles and Practice of Public Health Surveillance, 2nded.Oxford University Press, 2000. Ongoing, systematic collection, analysis, interpretation and dissemination of health-related data essential for public health practice (i.e. prevention and control of disease). Surveillance applies to both human and vetiranary diseases, may be general or sentinal, and may be active or passive. Surveillance may be for health events (such as deaths or disease), health services (vaccinations, hospital admissions), health behaviors (smoking, alcohol), or even risk factors (water supply, travel). Salwa Ali disease surveillance Salwa Ali Czechoslavakia Madkour's Brucellosis (Second Edition) 2000 by M. Monir Madkour salwa Ali Declared Brucellosis free in 1964. health services surveillance Salwa Ali infectious disease reemergence site Re-emerging infectious diseases are diseases that once were major health problems globally or in a particular country, and then declined dramatically, but are again becoming health problems for a significant proportion of the population. Salwa Ali SA brucellosis reemergence site These are countries or parts of countries where Brucellosis has reappeared after a significant decline in incidence SA SA Japan Since 1999, 11 cases in Japan have been reported. PMID: 20587207 Germany PMID: 18258041 Trends in the epidemiology of human brucellosis in Germany show that after a steady decrease in brucellosis incidence from 1962 to the 1980s, a persistent number of cases has been reported in recent years, with the highest incidence in Turkish immigrants. Bulgaria PMID: 19193282 Bulgaria had been free from brucellosis since 1958, but during 2005–2007, a reemergence of human and animal disease was recorded. Federation of Bosnia and Herzegovina Bosnia and Herzegovina was free of brucellosis from 1980 until 2000. Since then, the number of infected people in the country has rapidly increased, and infections have been recorded at almost the entire territory. In the recent years, brucellosis has been present continuously, with a changing morbidity rate and an overall tendency to increase. Thus, it has become an important public health problem in the country. PMC2931440 Salwa Ali B. abortus host role a role of being a B. abortus host. YL, YH vaccination surveillance Salwa Ali health behavior surveillance Salwa Ali http://www.cdc.gov/BRFSS/ Surveillance of certain health related behaviors i.e. smoking, alcohol or drug use. The Behavioral Risk Factor Surveillance System (BRFSS) is the world’s largest, on-going telephone health survey system, established by the CDC for tracking health conditions and risk behaviors in the United States yearly since 1984. environmental surveillance Salwa Ali Surveillance of environmental factors (ie. water, air, and food quaility) that may influence health, but independently of any health events associated with them. human disease surveillance animal disease surveillance infectious disease surveillance noninfectious disease surveillance Brucella containment SA YL biohazard containment that is for brucella syndromic surveillance http://www.webcitation.org/5LKEYsrRT According to a CDC definition, "the term 'syndromic surveillance' applies to surveillance using health-related data that precede diagnosis and signal a sufficient probability of a case or an outbreak to warrant further public health response. Though historically syndromic surveillance has been utilized to target investigation of potential cases, its utility for detecting outbreaks associated with bioterrorism is increasingly being explored by public health officials." Syndromic surveillance systems monitor data from school absenteeism logs, emergency call systems, hospitals' over-the-counter drug sale records, Internet searches, and other data sources to detect unusual patterns, alerting health professionals and pssibly anticipating a disease outbreak. Brucella canis host role a role of being a B. canis host. YL, YH Brucella melitensis host role a role of being a B. melitensis host. YL, YH Brucella cetaceae host role a role of being a B. cetaceae host. YL, YH Brucella neotomae host role YL, YH a role of being a B. neotomae host. Brucella ovis host role a role of being a B. ovis host. YL, YH Brucella pinnipediae host role a role of being a B. pinnipediae host. YL, YH process of establishing Brucella infection in macrophage a process of establishing Brucella infection in host when the host is a macrophage. YL, YH bioterrorism agent role a role of beign a bioterrorism agent YL, YH administrating doxycycline 100mg twice a day YL a antibiotic brucellosis treatment that uses doxycycline 100mg twice a day. administrating streptomycin 1g a day YL a antibiotic brucellosis treatment that uses sterptomycin 1g once a day. smooth Brucella lipopolysaccharide a Brucella lipopolysaccharide that has Brucella O polysaccharide as its intergal part rough Brucella lipopolysaccharide YL a Brucella lipopolysaccharide that has no 'O polysaccharide' as its part host-Brucella interaction To establish logical reasoning for a virulence factor, we developed five description rules as defined below. In the formulation of these rules, o denotes an organism O, g and g’ denote genetic materials, e denotes a molecular entity, p denotes a process, i denotes a host-pathogen interaction process, and mo denotes a mutant of O. (IR3) If o has_part g, ∩ g encodes e, then o has_part e IR3 means that if a molecular entity (i.e., gene product such as protein) is encoded by a gene from an organism, then this molecular entity is part of an organism. (IR4) If mo has_part g’, ∩ g’ derives_from g, ∩ ( g’ lacks_part part of g ∪ g lacks_part part of g’) ∩ genome of o has_part g, then genome of mo lacks_part g IR4 means that if a mutant of an organism has an artificially altered gene sequence g’ that is derived from g, either by an insertion or partial deletion, then the genome of the mutant has no intact g as its part. When the g is fully deleted from mutant mo (i.e., g gene knock-out), the above rule won’t apply. In this case, we simply assert that genome of mo lacks_part g (see below). (IR5) If genome of mo lacks_part g, then mo lacks_part g If the genome of mutant has no intact gene g as its part, the mutant has no g as its part. (IR6) If genome of mo lacks_part g, ∩ g encodes e, then mo lacks_part e IR6 means that if the mutant has no intact gene g as its part, and the gene g encodes the molecular entity e in the unmutated organism, then the mutant has no intact e as its part. IR7 was given as a final definition of virulence factor: (IR7) If (mo has disposition at some time attenuated disposition ∩ attenuated disposition realized in i) ∩ (mo lacks_part e ∪ mo lacks_part g), ∩ (mo agent_in_compromised_process p ∩ p part_of i), then e is_a virulence factor For example, as shown in Figure 5, (B. abortus eryC mutant lacks_part eryC ) AND (B. abortus eryC mutant agent_in_compromised_process intracellular replication in macrophage) AND (intracellular replication in macrophage part_of macrophage-Brucella interaction) means that EryC is_a Brucella virulence factor. We can therefore to identify the biological process important to the virulence during the host-Brucella interaction. For example, (EryC participate_in Brucella erythritol catabolic process) AND (EryC mutant of B. abortus agent_in_compromised_process intracellular replication in macrophage), which means that the Brucella erythritol catabolic process is crucial to the intracellular replication in macrophage. YL ‘host-Brucella interaction’ is ‘a process that Brucella and its host (host organism or host cell) have effects upon each other during the course of Brucella’s establishing the infection and the host’s responses in order to fight the infection’. All those processes fall into two categories: Brucella infect host process or host anit-Brucella process. Brucella virulence YL, YH the virulence from the Brucella bacterium Brucella T4SS effector role YL YL a role inheres in a Brucella protein or a DNA-complex upon which the Brucella T4SS acts, and it is realized in the processes where Brucella T4SS acts as an agent. Brucella T4SS effector YL YL a molecular entity that bears the Brucella T4SS substrate role. It is translocated or secreted by Brucellas T4SS. Brucella eryC gene Brucella erythritol catabolic process Erythritol catabolism by Brucella abortus. (Sperry JF, Robertson DC. J Bacteriol. 1975 Feb;121(2):619-30. ) http://jb.asm.org/content/121/2/619.full.pdf PMID: 163226 The metabolic process of Brucella that includes pathways and chemical reactions for Brucella to use erythritol as resource of sugar to support the intracellular growth. YL negative regulation of Brucella intracellular replication in macrophage Any process that stops, prevents, or reduces the frequency, rate or extent of the Brucella's l life cycle, the set of processes by which Brucella reproduces and spreads among macrophage cells. reduced intracellular replication in macrophage macrophage-smooth Brucella interaction A process that smooth Brucella and macrophage have effects upon each other during the course of smooth Brucella’s establishing the infection and the macrophage’s responses in order to fight the infection. macrophage-rough Brucella interaction A process that rough Brucella and macrophage have effects upon each other during the course of rough Brucella’s establishing the infection and the macrophage’s responses in order to fight the infection. dendritic cell-rough Brucella interaction A process that rough Brucella and dendritic cell have effects upon each other during the course of rough Brucella’s establishing the infection and the dendritic cell’s responses in order to fight the infection’. dendritic cell- smooth Brucella interaction A process that smooth Brucella and dendritic cell have effects upon each other during the course of Brucella’s establishing the infection and the dendritic cell’s responses in order to fight the infection’. epithelial cell - smooth Brucella interaction A process that smooth Brucella and epithelial cell have effects upon each other during the course of smooth Brucella’s establishing the infection and the epithelial cell’s responses in order to fight the infection’. epithelial cell - rough Brucella interaction A process that rough Brucella and epithelial cell have effects upon each other during the course of Brucella’s establishing the infection and the epithelial cell’s responses in order to fight the infection’. artificially mutated Brucella YL a proessed material that is generated by mutate one or more genes inside Brucella's genome, which results in the lack of experssion of those genes, and Brucella lacks the proteins encoded by mutated genes as its part. B. suis eyrC mutant MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Sangari et al., 2000]. see PMID:16177356,10708387 negative regulation of Brucella entry into host cell Any process that stops, prevents or reduces the rate of the biological process og Brucella enter into host cells. YL B. abortus BvrS/BvrR mutant PMID: 9701808; PMID: 16077108 acidification of BCV in macrophage macrophage antimicrobial peptide production a biological process where an antimicrobrial peptide is produced in a macrophage YL, YH antimicrobial peptide Brucella virB operon expression a biological process when Brucella virB operon genes are expressed negative regulation of smooth Brucella response to acidity inside BCV negative regulation of smooth Brucella response to nitrosative stress inside BCV negative regulation of smooth Brucella response to oxidative stress inside BCV positive regulation of smooth Brucella response to antimicrobial peptide negative regulation of smooth Brucella response to nurtient deprivation B. abortus sodC mutant MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [He et al., 2002]. See. PMID:11953393 mouse bone marrow-derived macrophage Brucella intracellular trafficking in macrophage The directed movement of Brucella within macrophage, which starts from internalization of Brucella by phagecytes and nonprofessional phagocytrs and leads to the developement of the replicative niche in the case of smooth Brucella, or lead to the killing of Brucella in the case of rought Brucella. YL paper in publish: Ontology-based representation and analysis of host-Brucella interactions smooth Brucella intracellular trafficking in macrophage The process starts with the engulfment of smooth Brucella into a macrophage, and ends with the formation of ER-derived replication niches of smooth Brucella vacuole. YL paper in publish: Ontology-based representation and analysis of host-Brucella interactions rough Brucella intracellular trafficking in macrophage The process starts from rough Brucella is engulfed by marcophage to the formation of a phagolysosome containing rough Brucella, where the bacterium is killed by macrophage. YL paper in publish: Ontology-based representation and analysis of host-Brucella interactions negative regulation of Brucella intracellular trafficking in macrophage B. abortus virB1 mutant See. PMID 15322008 B. abortus virB2 mutant MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. Brucella purine biosynthesis pathway GO:0006164 Brucella's chemical reactions and pathways resulting in the formation of a purine nucleotide, a compound consisting of nucleoside (a purine base linked to a deoxyribose or ribose sugar) esterified with a phosphate group at either the 3' or 5'-hydroxyl group of the sugar. YL subcalss of GO: purine nucleotide biosynthetic process (GO:0006164) B. abortus purE mutant See. PMID: 15271960 B. abortus purL mutant See. PMID: 15271960 B. abortus purD mutant MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. Like the purE mutant, a purD::Tn10 mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6485:Alcantara et al., 2004]. See. PMID: 15271960 B. abortus ilvD mutant See. PMID: 15271960 Brucella branched chain family amino acid biosynthetic process Brucellas's chemical reactions and pathways resulting in the formation of amino acids containing a branched carbon skeleton, comprising isoleucine, leucine and valine. GO:0009082 YL subclass of GO:0009082 B. abortus pncA mutant MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6469:Kim et al., 2003]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6469:Kim et al., 2003]. It indicates that the mutant has reduced virulence in mice. See. PMID:15135535 Brucella metabolic process GO:0008152 Brucella's chemical reactions and pathways, including anabolism and catabolism, by which living Brucella transform chemical substances. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. YL subclass of GO:metabolic process(GO:0008152) B. abortus zwf mutant MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Kim et al., 2003]. See PMID: 12761078 B. abortus hfq mutant MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6495:Sonnleitner et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6495:Sonnleitner et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6495:Sonnleitner et al., 2003]. See PMID:12730323 Brucella lipopolysaccharide biosynthetic process GO:0009103 Brucella's chemical reactions and pathways resulting in the formation of lipopolysaccharides, any of a group of related, structurally complex components of the outer membrane of Brucella. YL subcalss of GO:lipopolysaccharide biosynthetic process (GO:0009103) Brucella gntR5 mutant MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. See PMID:16113274 B. suis glyA mutant Serine hydroxymethyltransferase MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See. PMID:12438693 B. suis hisD mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisD gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See. PMID:12438693 B. suis leuA mutant MUTATION: leuA is a B. suis gene identified by signature-tagged mutagenesis. It is attenuated inside THP1 macrophage cell line. See. PMID:12438693 B. suis leuC mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis leuC gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See. PMID:12438693 B.suis lysA mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See. PMID:12438693 B.suis serB mutant See. PMID:12438693 Brucella glycine metabolic process GO:0006544 Brucella's chemical reactions and pathways involving glycine, aminoethanoic acid. subclass of GO:glycine metabolic process (GO:0006544) YL B. suis uppS mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See. PMID:12438693 B.suis miaA mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See. PMID:12438693 B. suis cobW mutant See. PMID:12438693 Brucella one-carbon metabolic process GO:0006730 subclass of GO: one-carbon metabolic process (GO:0006730) Brucella's chemical reactions and pathways involving the transfer of one-carbon units in various oxidation states. Brucella nucleotide metabolic process GO:0009117 Brucella's chemical reactions and pathways involving a nucleotide, a nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the glycose moiety; may be mono-, di- or triphosphate; this definition includes cyclic nucleotides (nucleoside cyclic phosphates). subclass of GO:nucleotide metabolic process (GO:0009117) Brucella tRNA processing GO:0008033 Brucella's process in which a pre-tRNA molecule is converted to a mature tRNA, ready for addition of an aminoacyl group. YL subclass of GO:tRNA processing (GO:0008033) Brucella glucose metabolic process GO:0006006 The glucose metabolic process happened within Brucella. subclass of GO:glucose metabolic process (GO:0006006) YL Brucella carbohydrate metabolic process GO:0005975 Brucella's chemical reactions and pathways involving carbohydrates, any of a group of organic compounds based of the general formula Cx(H2O)y. YL subcalss of GO:carbohydrate metabolic process (GO:0005975) B. abortus hemH mutant MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. See PMID:11553564 negative regulation of Brucella intracellular survival in macrophage decrease of intracellular live brucella in macrophage Brucella porphyrin-containing compound biosynthetic process GO:0006779 YL Brucella's chemical reactions and pathways resulting in the formation of any member of a large group of derivatives or analogs of porphyrin. Porphyrin consists of a ring of four pyrrole nuclei linked each to the next at their alpha positions through a methine group. subclass of GO: porphyrin-containing compound biosynthetic process (GO:0006779) Brucella heme biosynthetic process GO:0006783 Brucella's chemical reactions and pathways resulting in the formation of heme, any compound of iron complexed in a porphyrin (tetrapyrrole) ring, from less complex precursors. YL subclass of GO: heme biosynthetic process (GO:0006783) Brucella aromatic amino acid family biosynthetic process GO:0009073 subclass of GO: 0009073 brucella's chemical reactions and pathways resulting in the formation of aromatic amino acid family, amino acids with aromatic ring (phenylalanine, tyrosine, tryptophan). B. abortus bacA mutant B.suis pyc mutant B.suis pgi mutant See PMID:10678941 Brucella gluconeogenesis GO:0006094 The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol in Brucella subcalss of GO: gluconeogenesis (GO:0006094) Brucella glycolysis GO:0006096 Brucella's chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP. subclass of GO: glycolysis (GO:0006096) B. suis glnD mutant See PMID:10678941 B.suis rpsA mutant See PMID 10678941 translation process in Brucella YL subclass of GO: translation GO:0006412 the translation process that forms a Brucella protein. B.suis virB8 mutant See PMID ;10678941 macrophage lipid raft http://en.wikipedia.org/wiki/Lipid_raft The plasma membranes of marcophage contain combinations of glycosphingolipids and protein receptors, which is a part of cellular component and organized in glycolipoprotein microdomain. YL subclass of GO: membrane raft (GO:0045121) B.suis virB9 mutant See PMID:10510235 B.abortus virB10 mutant See PMID:10510235 B. abortus htrA mutant See PMID: 8890248 process of establishing Brucella infection in dendritic cell YL, YH a process of establishing Brucella infection in host when the host is a a dendritic cell. process of establishing Brucella infection in epithelial cell YL, YH a process of establishing Brucella infection in host when the host is an epithelial cell. macrophage - Brucella interaction A process that Brucella and macrophage have effects upon each other during the course of Brucella’s establishing the infection and the macrophage’s responses in order to fight the infection. host-Brucella interaction between macrophage and Brucella macrophage anti-Brucella process The process that is the part of the macrophage-Brucella interaction and has macrophage as its agent. YL dendritic cell - Brucella interaction A process that Brucella and dendritic cell have effects upon each other during the course of Brucella’s establishing the infection and the dendritic cell’s responses in order to fight the infection. epithelial cell - Brucella interaction A process that Brucella and epithelial cell have effects upon each other during the course of Brucella’s establishing the infection and the epithelial cell’s responses in order to fight the infection. smooth LPS and macrophage lipid raft interaction The chemical action and protien bindings involved in smooth Brucella LPS interacting with marcophage lipif raft, which lead to the engulfment of smooth Brucella into a macrophage. YL engulfment of smooth Brucella by macrophage YL the process of macrophage internalizing of smooth Brucella, that is immediately happened after the smooth LPS and macrophage lipid raft interaction process. engulfment of Brucella by macrophage YL the biological process of macrophage internalizing Brucella engulfment of rough Brucella by macrophage The process of macrophage internalizing rough Brucella. YL formation of early phagosome containing smooth Brucella YL, YH The process of forming an early phagosome containing smooth Brucella. formation of intermediate smooth Brucella containing phagosome The process of forming a intermediate smooth Brucella containing phagosome that will lead to formation of the intracellular replication niche of smooth Brucella. YL acidification of smooth Brucella containing phagosome GO:0090383 The process that reduce the PH of the smooth Brucella containing phagosome, measured by the concentration of the hydrogen ion. YL subclass of GO:phagosome acidification (GO:0090383) smooth Brucella containing phagosome fusion with ER membrane YL the process of smooth Brucella containing phagosome membrane fused with the ER membrane. This process will lead to the formationof ER-derived replication niche of smooth Brucella. smooth Brucella intracellular replication in macrophage The replication of smooth Brucella within macrophage. early phagosome containing smooth Brucella intermediate phagosome containing smooth Brucella acidic phagosome containing smooth Brucella ER-derived replication niche of smooth Brucella replicative phagosome containing smooth Brucella smooth Brucella entry into macrophage The process in which smooth Brucella enters a macrophage. YL rough Brucella entry into macrophage The process in which rough Brucella enters a macrophage. YL smooth Brucella relsease from macrophage The process of replicated smooth Brucella leaving the marcophage, and starts to invade other host cells inside host. YL formation of early phagosome containing rough Brucella The process of forming an early phagosome containing rough Brucella. YL maturation of phagsome containing rough Brucella GO:0090382 A process that is carried out at the cellular level which results in the arrangement of constituent parts of phagosome containing rough Brucella within a macrophage. Phagosome maturation begins with endocytosis and formation of the early phagosome and ends with the formation of the hybrid organelle, the phagolysosome. YL subclass of GO: phagosome maturation (GO:0090382) phagosome containing rough Brucella fusion with lysosome GO:0090385 The creation of a phagolysosome from a phagosome that contains rough Brucella and a lysosome. YL subclass of GO:phagosome-lysosome fusion (GO:0090385) macrophage killing of Brucella YL The process of removal of intracellular Brucella by a marcophage after it fuses with lysosome. early phagosome containing rough Brucella phagolysosome containing rough Brucella Brucella resistance to nutrient deprivation A protective resistance disposition of Brucella that is in virtue of Brucella's survival when it encounters the nutrient depriving intracellular enviroment. YL Brucella resistance to antimicrobial peptide The protective disposition of the Brucella when antimicrobial peptide is present, which normally initiate the killing bacteria process in other specices, which in virtue of Brucella's intrcellular survival. YL http://www.ncbi.nlm.nih.gov/pubmed/7622230 The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides. Martínez de Tejada G, Pizarro-Cerdá J, Moreno E, Moriyón I. Infect Immun. 1995 Aug;63(8):3054-61. PMID: 7622230 Brucella resistance to oxidative stress YL, YH a protective resistance disposition that is specific for Brucella resistance to host oxidative stress Brucella resistance to nitrosative stress The protective disposition of Brucella while exposed to high level of nitric oxide (NO) rich enviroment, or the highly reactive oxidant peroxynitrite, which is produced following interaction of NO with superoxide anions. This disposition is in virtue of Brucella's intrcellular survival. YL, YH Brucella resistance to acidic stress A protective resistance of Brucella that in virtue of Brucella's survival when exposured to a low pH acidic enviroment, such as inside a marcophage. YL smooth Brucella resistance to nutrient deprivation a biological process where smooth Brucella resists a nutrient deprivation. YL, YH smooth Brucella resistance to antimicrobial peptide a biological process where smooth Brucella resists an anticrobial peptide. YL, YH smooth Brucella resistance to oxidative stress inside BCV YL, YH a biological process where smooth Brucella resists an oxidative stress inside a Brucella-containing vacuole (BCV) smooth Brucella resistance to nitrosative stress inside BCV YL Any process that results in Brucella's resistance to the nitrosative stress within macrophage. Nitrosative stress is a state often resulting from exposure to high levels of nitric oxide (NO) or the highly reactive oxidant peroxynitrite, which is produced following interaction of NO with superoxide anions.NO was identified as the effector molecule in killing a range of intracellular pathogens. GO:0051409 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC108054/ smooth Brucella resistance to aicidity inside BCV A place holder for many processes that involved in the Brucella's protecitve response to the acidified intracellular enviroment. For example, YL Brucella containing vacuole BCV smooth Brucella containing vacuole translocation of RicA into macrophage YL, YH a biological process when RicA is translocated into a macrophage enzyme substrate role A role that inheres in a protein or a compound upon which enzyme catalyzes. It is realized in the enzymatic reaction processes, where the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. YL Brucella type IV secretion system T4SS, Brucella In Brucella, the VirB T4SS permits the injection of bacterial effectors inside host cells, leading to subversion of signaling pathways and favoring bacterial growth and pathogenesis. The virB operon promoter is tightly regulated by a combination of transcriptional activators and repressors that are expressed according to the environmental conditions encountered by Brucella. Recent advances have shed light on the Brucella T4SS regulatory mechanisms and also its substrates. Characterization of the targets and functions of these translocated effectors is underway and will help understand the role of the T4SS in the establishment of a replication niche inside host cells. [Brucella T4SS: the VIP pass inside host cells. Lacerda TL, Salcedo SP, Gorvel JP. Curr Opin Microbiol. 2013 Feb;16(1):45-51. doi: 10.1016/j.mib.2012.11.005. Epub 2013 Jan 11. Review. PMID: 23318140] Brucella T4SS The Brucella T4SS is composed of 11 Brucella virB proteins. regulation of Brucella intracellular trafficking whole-cell hybridization assay to detect Brucella YL Three fluorescent oligonucleotide probes from the 16S rRNA sequence of Brucella are used to diagnose human brucellosis. (Fernandez-Lago et al., 2000) disposition of uptaking erythritol as carbon source YL. the disposition of Brucella of using erythritol as carbon source, which is realized the the Brucella erythritol catabolic process. process of establishing Brucella infection in human a process of establishing Brucella infection in host when the host is a human. YL, YH process of establishing Brucella infection in mouse YL, YH a process of establishing Brucella infection in host when the host is a mouse. attenuated disposition A disposition of a pathogen becoming harmless or less virulent towards its host, when the pathogen is altered physically or genetically. This disposition is realized in the process of the pathogen-host interaction. It is host dependent, or host specific. YL, Y.H. http://en.wikipedia.org/wiki/Attenuated_vaccine host-pathogen interaction It is a oboselete term in GO, but we still need this term with regard to the domain of infectious disease. The term should belong to the IDO, or any other specific ontologies desrcibe the host and pathogen interactions. We temporarily put this term here. YL ‘a process that a pthogen and its host have effects upon each other while the pathogen’s establishing the infection in the host and the host’s responses in order to fight the infection’. B. suis rbsK mutant PMID:14979322 B. suis mgtB mutant Hela cell - Brucella interaction A process that Brucella and Hela cell have effects upon each other during the course of Brucella’s establishing the infection and the Hela cell's responses in order to fight the infection. YL mouse - Brucella interaction A process that Brucella and mouse have effects upon each other during the course of Brucella’s establishing the infection in mouse and the mouse’s defense responses. B. suis virB11 mutant Brucella intracellular survival Brucella's intracellular persistence The process of Brucella stay alive and keep a significant ratio inside host cell. YL negative regulation of Brucella intracellular survival decrease of intracellular live brucella B. abortus virB4 mutant See. PMID:15135535 negative regulation of Brucella intracellular survival in mouse decrease of intracellular live brucella in mpuse virulent disposition A disposition of a pathogen becoming extremely severe or harmful towards its host, when the pathogen is altered physically or genetically. This disposition is realized in the process of the pathogen-host interaction. It is host dependent, or host specific. YL negative regulation of Brucella intracellular survival in Hela cell decrease of intracellular live brucella in hela cell Brucella omp10 mutant Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Tibor et al., 2002]. see PMID:12228280 B. suis gnd mutant See PMID:12761078 gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Kim et al., 2003]. Brucella intracellular replication in Hela cell The replication of Brucella within Hela cell YL YL negative regulation of Brucella intracellular replication in Hela cell Any process that stops, prevents, or reduces the frequency, rate or extent of the Brucella's l life cycle, the set of processes by which Brucella reproduces and spreads among Hela cells. reduced intracellular replication in Hela cell negative regulation of Brucella intracellular replication pentose phosphate pathway Brucella vjbR mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella gtrB mutant MUTATION: Attenuated in Macrophages [:Delrue et al., 2004]. See PMID:14979322 Brucella deoR mutant MUTATION: Attenuated in Macrophages [Delrue et al., 2004]. See PMID:14979322 Brucella flgI mutant MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella gntR mutant MUTATION: Attenuated in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 B. abortus gluP mutant MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse [Essenberg et al., 2002]. See PMID:12414147 Brucella caiB mutant MUTATION: Attenuated in Macrophages [:Delrue et al., 2004]. See PMID:14979322 Brucella norE mutant MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 B.suis norD mutant MUTATION: A mutant of Brucella suis bearing a Tn5 insertion in norD , the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions (more-than-5log reduction in viable counts). As a consequence of the norD mutation , NO might not be further reduced to N2O by the NO reductase and it could become toxic for the bacteria. The infection of resting macrophages showed that the norD mutant and the wild-type strain displayed similar rates of multiplication. On the contrary, activation of J774A.1 cells by LPS and IFN was accompanied by a more-thantenfold attenuation of the norD mutant at 48 h p. i..[Loisel-Meyer et al., 2006]. See PMID:16495577 B. suis narG mutant MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis narG gene is required for intracellular multiplication in human macrophage THP-1 cells [Kohler et al., 2002]. See PMID:12438693 Brucella nrdH mutant MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Delrue et al., 2004]. See PMID:14979322 Brucella O-polysaccharide biosynthetic process Brucella's chemical reactions and pathways resulting in the formation of a O-polysaccharide, a polymer of many (typically more than 10) monosaccharide residues linked glycosidically. Brucella wbpW mutant MUTATION: Attenuated in Macrophages [Delrue et al., 2004]. See PMID:14979322 Brucella intracellular growth The increase in size or mass of Brucella inside its host cell. YL YL negative regulation of Brucella intracellular growth Brucella cydB mutant MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Endley et al., 2001]. See PMID:11274104 Brucella manB mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 negative regulation of Brucella entry into macrophage Brucella xfp mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella glycerol metabolic process GO:0006071 The chemical reactions and pathways involving glycerol, 1,2,3-propanetriol, a sweet, hygroscopic, viscous liquid, widely distributed in nature as a constituent of many lipids inside Brucella. YL Brucella glpK mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella cydD mutant MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Kim et al., 2003]. See PMID:12761078 Brucella cydC mutant MUTATION: Attenuated in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella rbsC mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella pcs mutant MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Conde-Alvarez et al., 2006]. See PMID:16882035 Brucella aidB mutant MUTATION: Attenuated in Macrophages. [Delrue et al., 2004]. See PMID:14979322 B. abortus pyrB mutant MUTATION: B. abortus pyrB (pyrimidines) gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Kim et al., 2003]. See PMID:12761078 negative regulation of Brucella intracellular growth in Hela cell decrease of intracellular live brucella in hela cell Brucella divK mutant MUTATION: Attenuated in Mice [Delrue et al., 2004]. See PMID:14979322 Brucella ugpB mutant MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Castañeda-Roldán et al., 2006]. See PMID:16817909 B. melitensis ugpA mutant MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Lestrate et al., 2003]. See PMID:14638795 Brucella RpiR mutant MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella gcvP mutant MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ficht, 2003]. See PMID:12523983 B. suis gcvT mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Kohler et al., 2002]. See PMID:12438693 B. melitensis xseA mutant MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Lestrate et al., 2003]. See PMID:14638795 Brucella galcD mutant MUTATION: Attenuated in Mice,Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella fdhA mutant MUTATION: Attenuated in Mice [Delrue et al., 2004]. See PMID:14979322 Brucella dacF mutant MUTATION: Attenuated in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella dppA mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 B. abortus znuA mutant MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [:Kim et al., 2003]. See. PMID:12761078 Brucella znuC mutant MUTATION: Attenuated in Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella flgE mutant MUTATION: Attenuated in Mice, but not Macrophage, Hela [Delrue et al., 2004]. See PMID:14979322 Brucella motB mutant MUTATION: Attenuated in Mice, but not Macrophage, Hela [Delrue et al., 2004]. See PMID:14979322 B.melitensis fliF mutant MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulence [Lestrate et al., 2003]. See PMID:14638795 B. abortus pheA mutant MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Alcantara et al., 2004]. See. PMID:15271960 B. abortus pgm mutant MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. This mutant is unable to survive in mice but replicates in HeLa cells, indicating that the complete LPS is not essential either for invasion or for intracellular multiplication. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. See PMID:10992476 B. abortus ilvD mutant MUTATION: Of those B abortus mutants with mini-Tn5 insertions in genes predicted to be involved in amino acid biosynthesis and transport, only the ilvD mutant, displayed attenuation in both macrophages and mice. The othre two amino acid biosynthesis mutants [trpB::miniTn5 and pheA::miniTn5] displayed wild-type virulence in mice but attenuated inside macrophages. The studies with B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not [Ref6485:Alcantara et al., 2004]. See PMID:15271960 Brucella ndvB mutant MUTATION: Attenuated in Mice, HeLa [PMID:14979322]. See PMID:14979322 Brucella glnD mutant MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. See PMID:10678941 Brucella cysI mutant MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [PMID:14979322]. See PMID:14979322 Brucella metH mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella malK mutant MUTATION: Attenuated in Macrophages, but not in HeLa [PMID:14979322]. See PMID:14979322 Brucella pgi mutant MUTATION: B. suis pgi is a gene identified by signature-tagged mutagenesis. The mutant is attenuated inside THP1 macrophages. The mutation of the pgi gene could also affect the biosynthesis of the bacterial peptidoglycan [Ref6484:Foulongne et al., 2000]. See PMID:10678941 B. suis pyrD mutant MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. See PMID:12761078 Brucella vsrB mutant FUNCTIONAL GROUP: Regulation [PMID:14979322]. FUNCTION: Histidine kinase [PMID:14979322]. MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella intracellular trafficking The directed movement of Brucella within host cell. YL B. suis aroC mutant MUTATION: The cloned aroC gene complements Escherichia coli and Salmonella enterica serovar Typhimurium aroC mutants. A B suis aroC mutant was found to be unable to grow in a defined medium without aromatic compounds. The mutant was highly attenuated in it issue culture (THP1 macrophages and HeLa cells) and murine virulence models [Ref6488:Foulongne et al., 2001]. See PMID:11119550 B. suis purF mutant MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. See PMID:12761078 Brucella tldD mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella thrC mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella wbpL mutant MUTATION: Attenuated in Mice, Macrophages [PMID:14979322]. See PMID:14979322 Brucella wbkB mutant See PMID:11081580 Brucella rfbD mutant MUTATION: Attenuated in Mice, Macrophages [PMID:14979322]. See PMID:14979322 Brucella perA mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella gmd mutant MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Moriyón et al., 2004]. See PMID:15099501 Brucella wbkA mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella pmm mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella wbpZ mutant MUTATION: Attenuated in Mice, Macrophages [PMID:14979322]. See PMID:14979322 Brucella feuP mutant MUTATION: Attenuated in Mice, Macrophages [PMID:14979322]. See PMID:14979322 Brucella feuQ mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella htrA mutant MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. See PMID:12438693 Brucella lpsA mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella pepN mutant MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. See PMID:12933870 Brucella spotT mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella omp25 mutant MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. See PMID:11447156 B. abortus purN mutant MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. See PMID:12761078 B. abortus purM mutant MUTATION: B. abortus purM gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. See PMID:12761078 Brucella galE mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 B. abortus purL mutant MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. Studies with B melitensis purE and B abortus purL mutants, which are purine auxotrophs, and B suis aroC mutants, which can not synthesize aromatic amino acids, indicate that the brucellae also face signicant nutrient limitation during their prolonged residence in host macrophages [Ref6485:Alcantara et al., 2004]. See PMID:15271960 B. melitensis tig mutant MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. See PMID:14638795 Brucella amiC mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella nifS mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella dsbA mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella artI mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 Brucella wbdA mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 B. suis glnA mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See PMID:12438693 Brucella cysK mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 B. abortus uvrA mutant MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. See PMID:16816190 Brucella lon mutant MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. See PMID:10672180 Brucella ntrY mutant MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. See PMID:10678941 B. suis ntrC mutant MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. See PMID:10373105 Brucella ppiD mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella virB operon promoter The Brucella operon promoter that initiates virB operon's transcription. The virB operon promoter is tightly regulated by a combination of transcriptional activators and repressors that are expressed according to the environmental conditions encountered by Brucella. [[Brucella T4SS: the VIP pass inside host cells. [Lacerda TL, Salcedo SP, Gorvel JP. Curr Opin Microbiol. 2013 Feb;16(1):45-51. doi: 10.1016/j.mib.2012.11.005. Epub 2013 Jan 11. Review. PMID: 23318140] Brucella recA mutant See PMID:12414170 Brucella rpoA mutant MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. See PMID:14638795 Brucella gloA mutant See PMID:14979322 B. melitensis cobB mutant MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. See PMID:14638795 Brucella ilvC mutant MUTATION: ilvC is one of the 37 mutants with virulene defect, screened out from the signature- tagged miniTn5 library [Ref6480:Lestrate et al., 2003]. See PMID:14638795 B. suis serB mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See PMID:12438693 VbjR - Brucella virB promoter binding http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897657/ YL, YH a Brucella virB promoter binding process when the binding molecule is VbjR. B. abortus aspC mutant MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. See PMID:12761078 Brucella lysR mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella pth mutant See PMID:15385478 Brucella dsbB mutant MUTATION: Attenuated in Mice, Macrophages [PMID:14979322]. See PMID:14979322 Brucella alkA mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella macA mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 B. suis dut mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See PMID:12438693 Brucella ansC mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella purE mutant MUTATION: Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALBc mouse model. It confirms the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages [Ref6485:Alcantara et al., 2004]. The purE mutant has reduced survival in murine macrophages and reduced virulence in mice [Ref6485:Alcantara et al., 2004]. A purE gene deletion mutant (purE201) of B melitensis was constructed as a potentially useful vaccine for humans and animals. At necropsy, bacteria were present in mammary lymph nodes or spleen of 33 of goats given virulent 16M but in none of goats given the purE mutant. The purE mutation of B melitensis 16M was stable and that the vaccine could be differentiated from wild-type strains by hybridization, purine auxotrophy, and kanamycin resistance. Mice clear the identical purE mutant strain from their spleens in only 8 weeks but remain infected with B. melitensis 16M for at least 3 months [Ref6485:Alcantara et al., 2004]. See PMID:15271960 B. suis pyc mutant MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. See PMID:10678941 Brucella livH mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 B. abortus purH mutant MUTATION: B. abortus mutant with mini-Tn5-disrupted purH displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. See PMID:15271960 B. abortus rplS mutant MUTATION: rplS is involved in translation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. See PMID:15271960 Brucella omp19 mutant MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. See PMID:12228280 Brucella hpt mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella hisC mutant MUTATION: hisC encodes for histidinol phosphate transaminase. Brucella hisC mutant showed very little reduction in number by 2 weeks post-inoculation, but was reduced by 8 weeks. See PMID:None B. suis hisF mutant MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis hisF gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. See PMID:12438693 Brucella bvrR mutant MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. See PMID:12218183 B. suis dnaK mutant MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. See PMID:11854256 Brucella pmtA mutant MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. See PMID:16882035 Brucella mutM mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 Brucella BMEI0085 mutant MUTATION: Attenuated in Macrophages [Delrue et al., 2004]. See PMID:14979322 Brucella gntR4 mutant MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. See PMID:16113274 Brucella pstP mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella mosC mutant MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella mgps mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella gntR2 mutant MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. See PMID:16113274 Brucella gntR17 mutant MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. See PMID:16113274 Brucella arsR6 mutant FUNCTIONAL GROUP: ArsR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. See PMID:16113274 Brucella BMEI0455 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella lpsB mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella trkH mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 Brucella carAB mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella bicA mutant MUTATION: Attenuated in Macrophages [Delrue et al., 2004]. See PMID:14979322 Brucella ilvI mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella aspB mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella BMEI0671 mutant MUTATION: Attenuated in Macrophages [Delrue et al., 2004]. See PMID:14979322 Brucella thrA mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 negative regulation of Brucella intracellular trafficking Brucella bvrS mutant MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. See PMID:16077108, 12414153, 9826346, 11401996, 12414149, 12218183 Brucella quorum sensing in macrophage a biological process when Brucella use a quorum sensing mechansim to sense and response to stress inside a macrophage. YL, YH Brucella virB promoter binding process a biological process when a Brucella virB promoter is bound. YL, YH Brucella cbbE mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 regulation of Brucella virB operon expression regulation of Brucella quorum sensing in macrophages Brucella BMEI1229 mutant MUTATION: Attenuated in Mice [Delrue et al., 2004]. See PMID:14979322 Brucella RicA and Rab2 binding Cell Microbiol. 2011 Jul;13(7):1044-58. doi: 10.1111/j.1462-5822.2011.01601.x. Epub 2011 May 30. Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2. de Barsy M(1), Jamet A, Filopon D, Nicolas C, Laloux G, Rual JF, Muller A, Twizere JC, Nkengfac B, Vandenhaute J, Hill DE, Salcedo SP, Gorvel JP, Letesson JJ, De Bolle X. Author information: (1)URBM, University of Namur (FUNDP), Belgium. Bacteria of the Brucella genus are facultative intracellular class III pathogens. These bacteria are able to control the intracellular trafficking of their vacuole, presumably by the use of yet unknown translocated effectors. To identify such effectors, we used a high-throughput yeast two-hybrid screen to identify interactions between putative human phagosomal proteins and predicted Brucella spp. proteins. We identified a specific interaction between the human small GTPase Rab2 and a Brucella spp. protein named RicA. This interaction was confirmed by GST-pull-down with the GDP-bound form of Rab2. A TEM-β-lactamase-RicA fusion was translocated from Brucella abortus to RAW264.7 macrophages during infection. This translocation was not detectable in a strain deleted for the virB operon, coding for the type IV secretion system. However, RicA secretion in a bacteriological culture was still observed in a ΔvirB mutant. In HeLa cells, a ΔricA mutant recruits less GTP-locked myc-Rab2 on its Brucella-containing vacuoles, compared with the wild-type strain. We observed altered kinetics of intracellular trafficking and faster proliferation of the B. abortusΔricA mutant in HeLa cells, compared with the wild-type control. Altogether, the data reported here suggest RicA as the first reported effector with a proposed function for B. abortus. © 2011 Blackwell Publishing Ltd. PMID: 21501366 [PubMed - indexed for MEDLINE] PMID: 21501366 The biological process that Brucella's RicA protein binding with human Rabs protien. YL de Barsy et al. observed that Brucella protein RicA encoded by gene BMEI0736 from B. abortus interacts with human small GTPase protein Rab2.(bru-interaction paper) IHF - Brucella virB promoter binding a Brucella virB promoter binding process when the binding molecule is IHF. YL, YH http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897657/ HutC - Brucella virB promoter binding a Brucella virB promoter binding process when the binding molecule is HutC. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897657/ YL, YH Brucella BMEI1258 mutant MUTATION: Attenuated in Differential fluorescence induction [Delrue et al., 2004]. See PMID:14979322 Brucella pyrC mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella intergarion host factor Brucella IHF a dimer of IHF alpha and IHF beta, a specific DNA-binding protein complex that functions in genetic recombination as well as in translational and transcriptional control. positive regulation of Brucella virB operon expression Brucella virB operon The Brucella operon that contains 12 genes necessary for Brucella Type IV seretion system. Brucella ery operon The Brucella operon that contains the ORFs for eryA, eryB, eryC and eryD. The first gene (eryA) encoded a 519 aa putative erythritol kinase. The second gene (eryB) encoded an erythritol phosphate dehydrogenase. The function of the third gene (eryC) product was tentatively assigned as D-erythrulose-1-phosphate dehydrogenase and the fourth gene (eryD) encoded a regulator of ery operon expression. The operon promoter was located 5' to eryA, and contained an IHF (integration host factor) binding site. Transcription from this promoter was repressed by EryD, and stimulated by erythritol. (http://www.ncbi.nlm.nih.gov/pubmed/10708387) YL The Brucella erythritol operon contains 4 ORFs for eryA, eryB, eryC and eryD respectively. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364660/) Brucella BMEI1339 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [Delrue et al., 2004]. See PMID:14979322 Brucella BMEI1361 mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella eryD gene Brucella ery operon expression a biological process where Brucella ery operon genes are expressed. YL, YH regulation of Brucella ery operon expression Any process that modulates the frequency, rate or extent of Brucella ery operon expression. Brucella uptaking erythritol as carbon resource YL the biological process of Brucella to utilize erythritol as its carbon resource when it grows inside its host cell, e.g. macrophages. Brucella operon Brucella operon is a functioning unit of Brucella genomic DNA containing a cluster of genes or ORF (open reading frame) under the control of a single promoter. Brucella BMEI1443 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella BMEI1448 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella operon promoter Conversely, in the presence of a repressor protein, this segment binds with the repressor. Because of this, the RNA polymerase cannot bind to it, resulting in the prevention of transcription of genes. And, this segment is now referred to as the operator gene. YL http://www.biology-online.org/dictionary/Promoter the Brucella promoter is the gene segment that serves as the initiation site where RNA polymerase binds to and initiates the transcription of certain genes. caspase-2 activation a biological process when caspase-2 is activated. YL, YH positive regulation of apoptotic programmed macrophage cell death Brucella dxps mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 disposition to host programmed cell death induced by Brucella infection YL the disposition of host cell that undergo programmed cell death triggered by Brucella infection Brucella resistance to host PCD YL, YH Brucella resistance to host programmed cell death a resistance disposition of host cell that in virtue of host cell's survival by not undergoing the programmed cell death when triggered by Brucella infection. Brucella BMEI1531 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella lysR18 mutant MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. See PMID:16113274 positive regulation of necrotic marcophage cell death apoptotic macrophage cell death apoptotic process(GO:0006915) YL A programmed cell death process happen in macrophage which begins when macrophage receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the macrophage cell into apoptotic bodies. When the execution phase is completed,macrophage has died. necrotic macrophage cell death A type of mcrophage cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. YL necrotic cell death (GO:0070265) Brucella BMEI1658 mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 process of establishing RB51 infection in macrophage YL, YH a process of establishing Brucella infection in macrophage when the Brucella is the RB51 vaccine strain. establishing virulent Brucella infection inside macrophage YL, YH a process of establishing Brucella infection in macrophage when the Brucella is a virulent strain. macrophage-RB51 interaction Brucella lysine biosynthesis process In plants and bacteria, it is synthesized from aspartic acid (aspartate). (http://en.wikipedia.org/wiki/Lysine_biosynthesis#Synthesis) Brucella glnL mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella entry into host cell Brucella BMEI1809 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella virulence process A pathogen virulence process where the pathogen is Brucella. YL. YH Brucella BMEI1844 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella intracellular survival in mouse a Brucella intracellular survival process when the host is a mouse Brucella cysY mutant MUTATION: Attenuated in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella BMEI1859 mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella BMEI1879 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella intracellular replication The intracellua reproduction of Brucella's new individuals that contain some portion of their genetic material inherited from Brucella. YL Brucella BMEI1902 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella lysR13 mutant MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. See PMID:16113274 host cell YL a cell that bears pathogen host role Brucella virb1 mutant MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6539:den et al., 2004]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6540:Sieira et al., 2000]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. See PMID:15322008, 10940027, 16113325, 16272371 B. abortus virb4 mutant MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6541:Watarai et al., 2002]. intracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6542:Kim et al., 2005]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. See PMID:11988518, 15869716, 15135535 B. abortus virb6 mutant MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. See PMID:None Brucella virb9 mutant MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6545:Rittig et al., 2001]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6546:Delrue et al., 2001]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. See PMID:11349069, 10510235, 11437834, 12414149 Brucella virb10 mutant MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6540:Sieira et al., 2000]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6547:Celli et al., 2003]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6463:Hong et al., 2000]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6538:Briones et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6548:Boschiroli et al., 2002]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. See PMID:10940027, 12925673, 10858227, 11401996, 12414154, 11260139 Brucella virb11 mutant MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. See PMID:15312849 Brucella gltD mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella nodV mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella mgtB mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella dhbC mutant MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes [PMID:14979322]. See PMID:14979322 Brucella rbsK mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella gntR10 mutant MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. See PMID:16113274 Brucella BMEII0128 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella pheB mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella fliC mutant MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella ftcR mutant MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria [Léonard et al., 2007]. See PMID:17056750 Brucella flghA mutant . MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella BMEII0274 mutant MUTATION: Attenuated in Macrophages [PMID:14979322]. See PMID:14979322 Brucella dbsA mutant MUTATION: Attenuated in HeLa [PMID:14979322]. See PMID:14979322 Brucella BMEII0318 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella BMEII0336 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella araG mutant MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [PMID:14979322]. See PMID:14979322 Brucella lysR12 mutant MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. See PMID:16113274 B. suis eryB mutant MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [:Sangari et al., 2000]. See PMID:10708387, 16177356 Brucella gntR1 mutant See PMID:16113274 Brucella nikA mutant MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [PMID:14979322]. See PMID:14979322 Brucella mocC mutant MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella fbpA mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 Brucella BMEII0626 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella ssuB mutant MUTATION: Attenuated in Differential fluorescence induction [PMID:14979322]. See PMID:14979322 Brucella BMEII0923 mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella nrdI mutant MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages [PMID:14979322]. See PMID:14979322 Brucella BMEII0935 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella BMEII1037 mutant MUTATION: Attenuated in Mice [PMID:14979322]. See PMID:14979322 Brucella BMEII1045 mutant MUTATION: Attenuated in Mice, Macrophages, HeLa [PMID:14979322]. See PMID:14979322 Brucella rpsA mutant See PMID:10678941 Brucella virB8 mutant MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. See PMID:10678941, 12414149 B. suis virB5 mutant MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. See PMID:12595417, 12595466, 16113325, 10510235 B. abortus virB3 mutant MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. See PMID:12761078 Brucella BMEI0066 mutant MUTATION: BMEI0066 deletion mutant fails to replicated in murine macrophages and is rapidly cleared from the spleens of experimentally infected BALB/c mice [Zhang et al., 2009]. See PMID:19742243 Brucella asp24 mutant MUTATION: A asp24 mutation in Brucella abortus is attenuated in mice [Kahl-McDonagh et al., 2007]. See PMID:17664263 B. melitensis bp26 mutant MUTATION: A bp26 mutant in Brucella melitensis was attenuated in mice [Cloeckaert et al., 2004]. See PMID:15246618 Brucella manAB mutant MUTATION: a manAB double mutant is attenuated in mice [Ref7375:Kahl-McDonagh and Ficht, 2006]. See PMID:16790778 Brucella pgk mutant MUTATION: A pgk mutant is attenuated in mice [Ref7376:Trant et al., 2010]. See PMID:20194591 6 weeks continuous doxycycline treatment duration of WHO standard for human brucellosis 42 a continous treatment duration that includes 6 weeks of deoxycycline treatment. It's part of a WHO standard treatment for human brucellosis. YL, YH 2 weeks continuous streptomycin treatment duration of WHO standard for human brucellosis 14 YL, YH a continous treatment duration that includes 2 weeks of streptomysin treatment. It's part of a WHO standard treatment for human brucellosis. 3 weeks continuous streptomycin treatment duration of WHO standard for human brucellosis 21 a continous treatment duration that includes 3 weeks of streptomysin treatment. It's part of a WHO standard treatment for human brucellosis. YL, YH Brucella protective antigen stimulated acquired immune response YL YL the adaptive immune response stimulated by Brucella protective antigen Brucella-specific protective T-cell mediated immune response The brucella protecitve antigen stimulated acquiref immune reponse that is mediated by T-cell YL YL B. suis 1330 rbsK mutant NCBIGene: 1164441 YH PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene rbsK. UniProtKB accession: Q8FXR0 The gene rbsK from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. suis 1330 mgtB mutant NCBIGene: 1164473 PMID: 14979322 YH A mutant of strain Brucella suis 1330 that lacks an intact gene mgtB. Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene mgtB from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FXM8 B. suis 1330 nodV mutant NCBIGene: 1164477 A mutant of strain Brucella suis 1330 that lacks an intact gene nodV. UniProtKB accession: Q8FXM4 The gene nodV from the strain Brucella suis 1330 is a virulence gene. PMID: 14979322 YH Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 gltD mutant YH UniProtKB accession: Q8FXL0 PMID: 10858227 Information about the mutated molecule: MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. A mutant of strain Brucella suis 1330 that lacks an intact gene gltD. NCBIGene: 1164492 The gene gltD from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 virB11 mutant A mutant of strain Brucella suis 1330 that lacks an intact gene virB11. UniProtKB accession: Q8FXK7 PMID: 15312849 YH NCBIGene: 1164496 Information about the mutated molecule: MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. The gene virB11 from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 virB10 mutant NCBIGene: 1164497 The gene virB10 from the strain Brucella suis 1330 is a virulence gene. YH UniProtKB accession: Q9RPX5 PMID: 11260139 A mutant of strain Brucella suis 1330 that lacks an intact gene virB10. Information about the mutated molecule: MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6465:Comerci et al., 2001]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6465:Comerci et al., 2001]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6465:Comerci et al., 2001]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6465:Comerci et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6465:Comerci et al., 2001]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. B. suis 1330 virB9 mutant Information about the mutated molecule: MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6466:Gorvel and Moreno, 2002]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6466:Gorvel and Moreno, 2002]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. UniProtKB accession: Q9RPX6 NCBIGene: 1164498 The gene virB9 from the strain Brucella suis 1330 is a virulence gene. PMID: 12414149 YH A mutant of strain Brucella suis 1330 that lacks an intact gene virB9. B. suis 1330 virB8 mutant A mutant of strain Brucella suis 1330 that lacks an intact gene virB8. NCBIGene: 1164499 UniProtKB accession: Q7CEG3 PMID: 12414149 Information about the mutated molecule: MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. The gene virB8 from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 virB6 mutant YH The gene virB6 from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1164501 Information about the mutated molecule: MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. UniProtKB accession: Q9RPX9 A mutant of strain Brucella suis 1330 that lacks an intact gene virB6. B. suis 1330 virB5 mutant PMID: 10510235 A mutant of strain Brucella suis 1330 that lacks an intact gene virB5. YH UniProtKB accession: Q9RPY0 NCBIGene: 1164502 The gene virB5 from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6467:O'Callaghan et al., 1999]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6467:O'Callaghan et al., 1999]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6467:O'Callaghan et al., 1999]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. B. suis 1330 virB4 mutant YH The gene virB4 from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6468:Kim et al., 2004]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6468:Kim et al., 2004]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene virB4. UniProtKB accession: Q9RPY1 NCBIGene: 1164503 PMID: 15135535 B. suis 1330 virB3 mutant The gene virB3 from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene virB3. YH NCBIGene: 1164504 Information about the mutated molecule: MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. UniProtKB accession: Q7CEG1 PMID: 12761078 B. suis 1330 virB2 mutant Information about the mutated molecule: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6470:Sun et al., 2005]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. The gene virB2 from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene virB2. YH UniProtKB accession: Q7CEG0 NCBIGene: 1164505 PMID: 16113325 B. suis 1330 virB1 mutant Information about the mutated molecule: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6471:Höppner et al., 2005]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6471:Höppner et al., 2005]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6471:Höppner et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. NCBIGene: 1164506 PMID: 16272371 The gene virB1 from the strain Brucella suis 1330 is a virulence gene. YH A mutant of strain Brucella suis 1330 that lacks an intact gene virB1. UniProtKB accession: Q9RPY4 B. suis 1330 hemH mutant YH UniProtKB accession: P0A3D7 NCBIGene: 1164513 Information about the mutated molecule: FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis PMID: last step(Swiss-Prot: P0A3D7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7). SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7). MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. The gene hemH from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene hemH. B. suis 1330 omp10 mutant A mutant of strain Brucella suis 1330 that lacks an intact gene omp10. YH Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane UniProtKB accession: P0A3N9 The gene omp10 from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1164514 PMID: lipid-anchor(Swiss-Prot: P0A3N9). MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9). SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9). MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. B. suis 1330 gnd mutant A mutant of strain Brucella suis 1330 that lacks an intact gene gnd. UniProtKB accession: Q8FXG6 YH The gene gnd from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1164548 PMID: 12761078 Information about the mutated molecule: MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. B. suis 1330 vjbR mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1164556 A mutant of strain Brucella suis 1330 that lacks an intact gene vjbR. PMID: 14979322 YH The gene vjbR from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FXF9 B. suis 1330 gtrB mutant A mutant of strain Brucella suis 1330 that lacks an intact gene gtrB. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8FXE4 NCBIGene: 1164572 PMID: 14979322 The gene gtrB from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 deoR mutant A mutant of strain Brucella suis 1330 that lacks an intact gene deoR. PMID: 14979322 YH UniProtKB accession: Q8FXD3 NCBIGene: 1164583 The gene deoR from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. suis 1330 flgI mutant A mutant of strain Brucella suis 1330 that lacks an intact gene flgI. UniProtKB accession: Q8FXC4 NCBIGene: 1164593 PMID: 14979322 YH Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: P-ring [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene flgI from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 gntR mutant YH PMID: 14979322 The gene gntR from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FXA3 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene gntR. NCBIGene: 1164614 B. suis 1330 caiB mutant NCBIGene: 1164661 The gene caiB from the strain Brucella suis 1330 is a virulence gene. YH PMID: 14979322 UniProtKB accession: Q8FX63 A mutant of strain Brucella suis 1330 that lacks an intact gene caiB. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. suis 1330 norE mutant PMID: 14979322 UniProtKB accession: Q8FX43 NCBIGene: 1164683 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene norE. YH The gene norE from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 norD mutant PMID: 16495577 NCBIGene: 1164688 A mutant of strain Brucella suis 1330 that lacks an intact gene norD. UniProtKB accession: Q8FX38 The gene norD from the strain Brucella suis 1330 is a virulence gene. YH Information about the mutated molecule: MUTATION: A mutant of Brucella suis bearing a Tn5 insertion in norD , the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions (more-than-5log reduction in viable counts). As a consequence of the norD mutation , NO might not be further reduced to N2O by the NO reductase and it could become toxic for the bacteria. The infection of resting macrophages showed that the norD mutant and the wild-type strain displayed similar rates of multiplication. On the contrary, activation of J774A.1 cells by LPS and IFN was accompanied by a more-thantenfold attenuation of the norD mutant at 48 h p. i. [Ref6475:Loisel-Meyer et al., 2006]. B. suis 1330 narG mutant NCBIGene: 1164736 YH Information about the mutated molecule: MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB accession: Q8FWZ3 The gene narG from the strain Brucella suis 1330 is a virulence gene. PMID: 12438693 A mutant of strain Brucella suis 1330 that lacks an intact gene narG. B. suis 1330 nrdH mutant PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene nrdH. YH The gene nrdH from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FWX8 NCBIGene: 1164751 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. B. suis 1330 wbpW mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1164785 PMID: 14979322 YH A mutant of strain Brucella suis 1330 that lacks an intact gene wbpW. The gene wbpW from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FWU8 B. suis 1330 manB mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene manB. NCBIGene: 1164786 The gene manB from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FWU7 PMID: 14979322 YH B. suis 1330 oxyR mutant The gene oxyR from the strain Brucella suis 1330 is a virulence gene. PMID: 10986275 A mutant of strain Brucella suis 1330 that lacks an intact gene oxyR. Information about the mutated molecule: MUTATION: The transcription product of Brucella abortus oxyR binds to the B abortus catalase promoter region. A gene replacementdeletion Brucella oxyR mutant exhibits increased sensitivity to prolonged exposure to H2O2 and is unable to adapt to H2O2 in the environment [Ref6476:Kim and Mayfield, 2000]. UniProtKB accession: Q8FWU1 YH NCBIGene: 1164792 B. suis 1330 xfp mutant UniProtKB accession: Q8FWR0 A mutant of strain Brucella suis 1330 that lacks an intact gene xfp. The gene xfp from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1164823 PMID: 14979322 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 glpK mutant The gene glpK from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FWK8 PMID: first (rate-limiting) step(Swiss-Prot: Q8FWK8). SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8). MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene glpK. Information about the mutated molecule: FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8). CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8). PATHWAY: Glycerol utilization YH NCBIGene: 1164881 B. suis 1330 ssuB mutant NCBIGene: 1164905 PMID: 14979322 YH UniProtKB accession: Q8FWI7 A mutant of strain Brucella suis 1330 that lacks an intact gene ssuB. The gene ssuB from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Permease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. B. suis 1330 cydD mutant UniProtKB accession: Q8FWE7 Information about the mutated molecule: MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. A mutant of strain Brucella suis 1330 that lacks an intact gene cydD. YH The gene cydD from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1164946 PMID: 12761078 B. suis 1330 cydC mutant PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene cydC. NCBIGene: 1164947 YH The gene cydC from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FWE6 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 cydB mutant PMID: 11274104 NCBIGene: 1164949 UniProtKB accession: Q8FWE4 The gene cydB from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene cydB. YH Information about the mutated molecule: MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. B. suis 1330 rbsC mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene rbsC. UniProtKB accession: Q8FW92 The gene rbsC from the strain Brucella suis 1330 is a virulence gene. PMID: 14979322 NCBIGene: 1165007 B. suis 1330 pcs mutant YH UniProtKB accession: Q8FW88 PMID: 16882035 NCBIGene: 1165011 Information about the mutated molecule: MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. The gene pcs from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene pcs. B. suis 1330 aidB mutant The gene aidB from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FW64 PMID: 14979322 NCBIGene: 1165038 YH Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene aidB. B. suis 1330 pyrB mutant The gene pyrB from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: P65612 NCBIGene: 1165039 A mutant of strain Brucella suis 1330 that lacks an intact gene pyrB. PMID: UMP biosynthesis Information about the mutated molecule: CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis YH B. suis 1330 divK mutant A mutant of strain Brucella suis 1330 that lacks an intact gene divK. NCBIGene: 1165052 UniProtKB accession: Q8FW53 PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. YH The gene divK from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 ugpB mutant UniProtKB accession: Q8FW10 NCBIGene: 1165097 Information about the mutated molecule: MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. A mutant of strain Brucella suis 1330 that lacks an intact gene ugpB. The gene ugpB from the strain Brucella suis 1330 is a virulence gene. PMID: 16817909 YH B. suis 1330 ugpA mutant The gene ugpA from the strain Brucella suis 1330 is a virulence gene. PMID: 14638795 UniProtKB accession: Q8FW09 NCBIGene: 1165098 YH A mutant of strain Brucella suis 1330 that lacks an intact gene ugpA. Information about the mutated molecule: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. B. suis BRA0692 mutant The gene BRA0692 from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene BRA0692. Information about the mutated molecule: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. YH PMID: 14638795 UniProtKB accession: Q8FVX6 NCBIGene: 1165134 B. suis 1330 fbpA mutant Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1165142 YH UniProtKB accession: Q8FVX0 PMID: 14979322 The gene fbpA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene fbpA. B. suis 1330 sodC mutant PMID: 11953393 Information about the mutated molecule: FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6481:He et al., 2002][Ref6481:He et al., 2002][Ref6481:He et al., 2002]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6481:He et al., 2002]. NCBIGene: 1165145 A mutant of strain Brucella suis 1330 that lacks an intact gene sodC. YH The gene sodC from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: P66827 B. suis 1330 RpiR mutant UniProtKB accession: Q8FVV9 The gene RpiR from the strain Brucella suis 1330 is a virulence gene. PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene RpiR. YH NCBIGene: 1165154 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 gcvP mutant YH UniProtKB accession: Q8FVU9 The gene gcvP from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor A mutant of strain Brucella suis 1330 that lacks an intact gene gcvP. PMID: CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-Prot: Q8FVU9). CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-Prot: Q8FVU9). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FVU9). SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-Prot: Q8FVU9). SIMILARITY: Belongs to the gcvP family(Swiss-Prot: Q8FVU9). MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ref6482:Ficht, 2003]. NCBIGene: 1165167 B. suis 1330 gcvT mutant YH A mutant of strain Brucella suis 1330 that lacks an intact gene gcvT. NCBIGene: 1165169 The gene gcvT from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB accession: Q8FVU8 PMID: 12438693 B. suis 1330 xseA mutant A mutant of strain Brucella suis 1330 that lacks an intact gene xseA. The gene xseA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FVR1 YH Information about the mutated molecule: FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. NCBIGene: 1165206 PMID: 14638795 B. suis 1330 zwf mutant PMID: 12761078 YH A mutant of strain Brucella suis 1330 that lacks an intact gene zwf. NCBIGene: 1165220 Information about the mutated molecule: MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. UniProtKB accession: Q8FVP8 The gene zwf from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 nikA mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1165246 YH UniProtKB accession: F8WJW5 The gene nikA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene nikA. B. suis 1330 galcD mutant A mutant of strain Brucella suis 1330 that lacks an intact gene galcD. NCBIGene: 1165248 YH UniProtKB accession: Q8FVM8 The gene galcD from the strain Brucella suis 1330 is a virulence gene. PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 eryB mutant PMID: 10708387 A mutant of strain Brucella suis 1330 that lacks an intact gene eryB. NCBIGene: 1165308 UniProtKB accession: Q8FVH6 The gene eryB from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6483:Sangari et al., 2000]. YH B. suis 1330 ugpA mutant NCBIGene: 1165309 UniProtKB accession: Q8FVH5 The gene eryC from the strain Brucella suis 1330 is a virulence gene. YH PMID: 10708387 Information about the mutated molecule: MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6483:Sangari et al., 2000]. A mutant of strain Brucella suis 1330 that lacks an intact gene eryC. B. suis 1330 fdhA mutant UniProtKB accession: Q8FVC5 A mutant of strain Brucella suis 1330 that lacks an intact gene fdhA. PMID: 14979322 NCBIGene: 1165363 YH Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. The gene fdhA from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 araG mutant NCBIGene: 1165380 UniProtKB accession: Q8FVA9 PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene araG. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. YH The gene araG from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 dacF mutant UniProtKB accession: Q8FV99 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene dacF. YH The gene dacF from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1165391 PMID: 14979322 B. suis 1330 cobW mutant YH The gene cobW from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene cobW. NCBIGene: 1165431 PMID: 12438693 UniProtKB accession: Q8FV62 Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. B. suis 1330 dppA mutant A mutant of strain Brucella suis 1330 that lacks an intact gene dppA (not ortho to BRUME). YH PMID: 14979322 The gene dppA (not ortho to BRUME) from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1165456 UniProtKB accession: Q8FV39 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 znuA mutant A mutant of strain Brucella suis 1330 that lacks an intact gene znuA. YH Information about the mutated molecule: MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. PMID: 12761078 NCBIGene: 1165575 The gene znuA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FUU6 B. suis 1330 znuC mutant A mutant of strain Brucella suis 1330 that lacks an intact gene znuC. The gene znuC from the strain Brucella suis 1330 is a virulence gene. PMID: 14979322 YH NCBIGene: 1165576 UniProtKB accession: Q8FUU5 Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 flgE mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1165592 The gene flgE from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FUS9 A mutant of strain Brucella suis 1330 that lacks an intact gene flgE. YH B. suis 1330 motB mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene motB. NCBIGene: 1165597 UniProtKB accession: Q8FUS5 The gene motB from the strain Brucella suis 1330 is a virulence gene. YH PMID: 14979322 B. suis 1330 fliF mutant NCBIGene: 1165599 The gene fliF from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene fliF. YH UniProtKB accession: Q8FUS3 Information about the mutated molecule: FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane PMID: multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3). SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3). MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. B. suis 1330 rpsA mutant YH A mutant of strain Brucella suis 1330 that lacks an intact gene rpsA. The gene rpsA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G3C2 PMID: 10678941 Information about the mutated molecule: MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. NCBIGene: 1165684 B. suis 1330 pheA mutant PMID: 15271960 YH NCBIGene: 1165694 A mutant of strain Brucella suis 1330 that lacks an intact gene pheA. Information about the mutated molecule: MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. The gene pheA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G3B3 B. suis 1330 pgm mutant PMID: 10992476 UniProtKB accession: Q8G392 The gene pgm from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1165715 YH Information about the mutated molecule: MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. A mutant of strain Brucella suis 1330 that lacks an intact gene pgm. B. suis 1330 ilvD mutant NCBIGene: 1165756 PMID: L-isoleucine biosynthesis Information about the mutated molecule: CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella suis 1330 that lacks an intact gene ilvD. The gene ilvD from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G353 YH B. suis 1330 ndvB mutant NCBIGene: 1165768 The gene ndvB from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 UniProtKB accession: Q8G341 A mutant of strain Brucella suis 1330 that lacks an intact gene ndvB. B. suis 1330 glnD mutant A mutant of strain Brucella suis 1330 that lacks an intact gene glnD. UniProtKB accession: Q8G312 PMID: 10678941 NCBIGene: 1165801 Information about the mutated molecule: FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312). CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312). SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312). MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. The gene glnD from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 cysI mutant NCBIGene: 1165838 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. YH The gene cysI from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G2X8 A mutant of strain Brucella suis 1330 that lacks an intact gene cysI. PMID: 14979322 B. suis 1330 metH mutant UniProtKB accession: Q8G2X1 PMID: 14979322 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene metH. NCBIGene: 1165845 The gene metH from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 malK mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene malK. NCBIGene: 1165896 UniProtKB accession: Q8G2S6 The gene malK from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 hisD mutant UniProtKB accession: Q8G2R2 A mutant of strain Brucella suis 1330 that lacks an intact gene hisD. The gene hisD from the strain Brucella suis 1330 is a virulence gene. PMID: L-histidine biosynthesis Information about the mutated molecule: FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis YH NCBIGene: 1165911 B. suis 1330 pgi mutant The gene pgi from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G2N3 A mutant of strain Brucella suis 1330 that lacks an intact gene pgi. PMID: glycolysis Information about the mutated molecule: CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation NCBIGene: 1165946 YH B. suis 1330 pyrD mutant YH UniProtKB accession: Q8G2K8 The gene pyrD from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1165972 Information about the mutated molecule: MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. A mutant of strain Brucella suis 1330 that lacks an intact gene pyrD. PMID: 12761078 B. suis 1330 vsrB mutant PMID: 14979322 YH NCBIGene: 1165977 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene vsrB. The gene vsrB from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G2K3 B. suis 1330 bacA mutant Information about the mutated molecule: MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. The gene bacA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G2F1 YH A mutant of strain Brucella suis 1330 that lacks an intact gene bacA. PMID: 10741969 NCBIGene: 1166033 B. suis 1330 purD mutant NCBIGene: 1166075 PMID: IMP biosynthesis Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis A mutant of strain Brucella suis 1330 that lacks an intact gene purD. UniProtKB accession: Q8G2B1 The gene purD from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 aroC mutant PMID: chorismate biosynthesis Information about the mutated molecule: CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis YH A mutant of strain Brucella suis 1330 that lacks an intact gene aroC. UniProtKB accession: P63608 NCBIGene: 1166089 The gene aroC from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 exsA mutant The gene exsA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene exsA. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIGene: 1166103 YH UniProtKB accession: Q8G286 B. suis 1330 purF mutant NCBIGene: 1166107 A mutant of strain Brucella suis 1330 that lacks an intact gene purF. YH Information about the mutated molecule: MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. The gene purF from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G282 PMID: 12761078 B. suis 1330 tldD mutant Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1166126 YH PMID: 14979322 UniProtKB accession: Q8G266 A mutant of strain Brucella suis 1330 that lacks an intact gene tldD. The gene tldD from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 thrC mutant PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene thrC. UniProtKB accession: Q8G249 The gene thrC from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166145 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. suis 1330 dsbA mutant The gene dsbA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G237 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 NCBIGene: 1166157 A mutant of strain Brucella suis 1330 that lacks an intact gene dsbA. B. suis 1330 wbpL mutant NCBIGene: 1166172 PMID: 14979322 YH The gene wbpL from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G225 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene wbpL. B. suis 1330 wbkB mutant YH Information about the mutated molecule: MUTATION: No function has been assigned to the B. melitensis 16M wbkB gene either by homology search or functionally, because deletion of wbkB did not interfere with the O-antigen structure [Ref6489:Godfroid et al., 2000]. NCBIGene: 1166180 UniProtKB accession: Q8G223 A mutant of strain Brucella suis 1330 that lacks an intact gene wbkB. The gene wbkB from the strain Brucella suis 1330 is a virulence gene. PMID: 11081580 B. suis 1330 rfbD mutant PMID: 14979322 YH UniProtKB accession: Q8G221 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene rfbD. The gene rfbD from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166182 B. suis 1330 perA mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB accession: Q8G220 A mutant of strain Brucella suis 1330 that lacks an intact gene perA. YH The gene perA from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166183 B. suis 1330 gmd mutant The gene gmd from the strain Brucella suis 1330 is a virulence gene. YH PMID: 15099501 UniProtKB accession: Q8G219 NCBIGene: 1166184 Information about the mutated molecule: MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene gmd. B. suis 1330 wbkA mutant A mutant of strain Brucella suis 1330 that lacks an intact gene wbkA. The gene wbkA from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166191 UniProtKB accession: Q8G218 YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. B. suis 1330 pmm mutant UniProtKB accession: Q8G214 NCBIGene: 1166199 The gene pmm from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene pmm. PMID: 14979322 YH B. suis 1330 wbpZ mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. The gene wbpZ from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene wbpZ. YH NCBIGene: 1166202 PMID: 14979322 UniProtKB accession: Q8G211 B. suis 1330 feuP mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene feuP. NCBIGene: 1166266 YH PMID: 14979322 UniProtKB accession: Q8G1U9 The gene feuP from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 feuQ mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene feuQ. PMID: 14979322 UniProtKB accession: Q8G1U8 NCBIGene: 1166267 YH The gene feuQ from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 htrA mutant NCBIGene: 1166273 Information about the mutated molecule: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002]. FUNCTION: Protease [Ref412:Kohler et al., 2002]. MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. PMID: 12438693 The gene htrA from the strain Brucella suis 1330 is a virulence gene. YH UniProtKB accession: P0A3Z5 A mutant of strain Brucella suis 1330 that lacks an intact gene htrA. B. suis 1330 lpsA mutant NCBIGene: 1166277 A mutant of strain Brucella suis 1330 that lacks an intact gene lpsA. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH The gene lpsA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G1T9 B. suis 1330 pepN mutant PMID: 12933870 Information about the mutated molecule: MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. YH NCBIGene: 1166279 A mutant of strain Brucella suis 1330 that lacks an intact gene pepN. The gene pepN from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G1T7 B. suis 1330 spotT mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene spotT from the strain Brucella suis 1330 is a virulence gene. YH NCBIGene: 1166315 UniProtKB accession: Q8CY42 A mutant of strain Brucella suis 1330 that lacks an intact gene spotT. B. suis 1330 omp25 mutant A mutant of strain Brucella suis 1330 that lacks an intact gene omp25. YH Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689). SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689). MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. UniProtKB accession: Q45689 The gene omp25 from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166364 PMID: 11447156 B. suis 1330 purN mutant PMID: 12761078 UniProtKB accession: G0K8C8 NCBIGene: 1166372 Information about the mutated molecule: MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. YH A mutant of strain Brucella suis 1330 that lacks an intact gene purN. The gene purN from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 purM mutant Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis NCBIGene: 1166373 A mutant of strain Brucella suis 1330 that lacks an intact gene purM. UniProtKB accession: Q8G1K5 YH The gene purM from the strain Brucella suis 1330 is a virulence gene. PMID: IMP biosynthesis B. suis 1330 pepN mutant NCBIGene: 1166378 The gene galE from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G1K0 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene galE. YH PMID: 14979322 B. suis 1330 glyA mutant PMID: 12438693 UniProtKB accession: Q8G1F1 The gene glyA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene glyA. NCBIGene: 1166430 YH Information about the mutated molecule: FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. B. suis 1330 purL mutant YH The gene purL from the strain Brucella suis 1330 is a virulence gene. PMID: IMP biosynthesis UniProtKB accession: Q8G183 A mutant of strain Brucella suis 1330 that lacks an intact gene purL. NCBIGene: 1166505 Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183). PATHWAY: Nucleotide biosynthesis B. suis 1330 tig mutant YH The gene tig from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166567 UniProtKB accession: Q8G129 Information about the mutated molecule: FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. A mutant of strain Brucella suis 1330 that lacks an intact gene tig. PMID: 14638795 B. suis 1330 dsbA mutant Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8G119 YH A mutant of strain Brucella suis 1330 that lacks an intact gene dsbA. NCBIGene: 1166578 PMID: 14979322 The gene dsbA from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 amiC mutant A mutant of strain Brucella suis 1330 that lacks an intact gene amiC. NCBIGene: 1166584 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene amiC from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G113 PMID: 14979322 YH B. suis 1330 nifS mutant NCBIGene: 1166599 YH Information about the mutated molecule: FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004]. FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8G101 A mutant of strain Brucella suis 1330 that lacks an intact gene nifS. PMID: 14979322 The gene nifS from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 dsbA mutant The gene dsbA from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH UniProtKB accession: Q8G0Z8 NCBIGene: 1166602 A mutant of strain Brucella suis 1330 that lacks an intact gene dsbA. B. suis 1330 artI mutant NCBIGene: 1166625 A mutant of strain Brucella suis 1330 that lacks an intact gene artI. YH UniProtKB accession: Q8G0X7 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 The gene artI from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 wbdA mutant A mutant of strain Brucella suis 1330 that lacks an intact gene wbdA. UniProtKB accession: Q8G0V3 The gene wbdA from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166655 YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. suis 1330 glnA mutant The gene glnA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G0T3 PMID: 12438693 NCBIGene: 1166677 YH A mutant of strain Brucella suis 1330 that lacks an intact gene glnA. Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. B. suis 1330 cysK mutant Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene cysK. UniProtKB accession: Q8G0N6 The gene cysK from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166727 YH PMID: 14979322 B. suis 1330 caiB mutant NCBIGene: 1166760 UniProtKB accession: Q8G0K8 A mutant of strain Brucella suis 1330 that lacks an intact gene caiB. The gene caiB from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH B. suis 1330 uvrA mutant UniProtKB accession: Q8G0I9 YH PMID: 16816190 NCBIGene: 1166780 Information about the mutated molecule: FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. The gene uvrA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene uvrA. B. suis 1330 lon mutant The gene lon from the strain Brucella suis 1330 is a virulence gene. PMID: 10672180 YH A mutant of strain Brucella suis 1330 that lacks an intact gene lon. NCBIGene: 1166782 Information about the mutated molecule: FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7). CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7). SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7). SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7). MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. UniProtKB accession: Q8G0I7 B. suis 1330 hfq mutant PMID: 14521880 Information about the mutated molecule: FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6495:Sonnleitner et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6495:Sonnleitner et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6495:Sonnleitner et al., 2003]. The gene hfq from the strain Brucella suis 1330 is a virulence gene. YH NCBIGene: 1166787 A mutant of strain Brucella suis 1330 that lacks an intact gene hfq. UniProtKB accession: P0A3G8 B. suis 1330 ntrY mutant NCBIGene: 1166792 Information about the mutated molecule: MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. PMID: 10678941 A mutant of strain Brucella suis 1330 that lacks an intact gene ntrY. UniProtKB accession: Q8G0H8 The gene ntrY from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 ntrC mutant The gene ntrC from the strain Brucella suis 1330 is a virulence gene. YH A mutant of strain Brucella suis 1330 that lacks an intact gene ntrC. UniProtKB accession: Q8G0H7 PMID: 10373105 NCBIGene: 1166793 Information about the mutated molecule: MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. B. suis 1330 ppiD mutant A mutant of strain Brucella suis 1330 that lacks an intact gene ppiD. UniProtKB accession: Q8G0F6 PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004]. FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1166815 YH The gene ppiD from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 uppS mutant NCBIGene: 1166834 Information about the mutated molecule: FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9). CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9). COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9). SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. YH A mutant of strain Brucella suis 1330 that lacks an intact gene uppS. UniProtKB accession: Q8G0D9 The gene uppS from the strain Brucella suis 1330 is a virulence gene. PMID: 12438693 B. suis 1330 recA mutant The gene recA from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1166878 A mutant of strain Brucella suis 1330 that lacks an intact gene recA. YH PMID: 12414170 UniProtKB accession: P65976 Information about the mutated molecule: FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6497:Halling, 2002]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6497:Halling, 2002]. B. suis 1330 rpoA mutant UniProtKB accession: Q8G094 NCBIGene: 1166885 A mutant of strain Brucella suis 1330 that lacks an intact gene rpoA. YH Information about the mutated molecule: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. The gene rpoA from the strain Brucella suis 1330 is a virulence gene. PMID: 14638795 B. suis 1330 gloA mutant UniProtKB accession: Q8G047 A mutant of strain Brucella suis 1330 that lacks an intact gene gloA. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1166947 The gene gloA from the strain Brucella suis 1330 is a virulence gene. YH PMID: 14979322 B. suis 1330 cobB mutant PMID: 14638795 A mutant of strain Brucella suis 1330 that lacks an intact gene cobB. Information about the mutated molecule: FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020). PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020). SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020). MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. The gene cobB from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8G020 YH NCBIGene: 1166977 B. suis 1330 aspB mutant YH A mutant of strain Brucella suis 1330 that lacks an intact gene aspB. PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1167060 UniProtKB accession: Q8FZU3 The gene aspB from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 ilvC mutant PMID: L-isoleucine biosynthesis YH UniProtKB accession: Q8FZU1 A mutant of strain Brucella suis 1330 that lacks an intact gene ilvC. Information about the mutated molecule: CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). PATHWAY: Amino-acid biosynthesis NCBIGene: 1167062 The gene ilvC from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 miaA mutant NCBIGene: 1167072 PMID: 12438693 The gene miaA from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8CY40 YH Information about the mutated molecule: FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. A mutant of strain Brucella suis 1330 that lacks an intact gene miaA. B. suis 1330 serB mutant YH Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB accession: Q8FZT1 PMID: 12438693 The gene serB from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene serB. NCBIGene: 1167073 B. suis 1330 pncA mutant The gene pncA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene pncA. PMID: 12761078 YH UniProtKB accession: Q8FZL6 NCBIGene: 1167146 Information about the mutated molecule: MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6469:Kim et al., 2003]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6469:Kim et al., 2003]. It indicates that the mutant has reduced virulence in mice. B. suis 1330 pncA mutant NCBIGene: 1167147 A mutant of strain Brucella suis 1330 that lacks an intact gene pncA. The gene pncA from the strain Brucella suis 1330 is a virulence gene. PMID: 12761078, 15135535 UniProtKB accession: Q8FZL5 Information about the mutated molecule: MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. YH B. suis 1330 aspC mutant YH A mutant of strain Brucella suis 1330 that lacks an intact gene aspC. NCBIGene: 1167178 UniProtKB accession: Q8FZI6 The gene aspC from the strain Brucella suis 1330 is a virulence gene. PMID: 12761078 Information about the mutated molecule: MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. B. suis 1330 lysR mutant UniProtKB accession: Q8FZI3 YH PMID: 14979322 The gene lysR from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene lysR. NCBIGene: 1167181 B. suis 1330 pth mutant A mutant of strain Brucella suis 1330 that lacks an intact gene pth. UniProtKB accession: P65864 Information about the mutated molecule: FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. The gene pth from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1167219 YH PMID: 15385478 B. suis 1330 leuA mutant Information about the mutated molecule: FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis The gene leuA from the strain Brucella suis 1330 is a virulence gene. PMID: L-leucine biosynthesis UniProtKB accession: Q8FZC4 NCBIGene: 1167249 A mutant of strain Brucella suis 1330 that lacks an intact gene leuA. YH B. suis 1330 dsbB mutant NCBIGene: 1167334 UniProtKB accession: Q8FZ55 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene dsbB. PMID: 14979322 The gene dsbB from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 alkA mutant YH NCBIGene: 1167338 The gene alkA from the strain Brucella suis 1330 is a virulence gene. PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene alkA. UniProtKB accession: Q8FZ51 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 macA mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella suis 1330 that lacks an intact gene macA. YH NCBIGene: 1167364 UniProtKB accession: Q8FZ29 The gene macA from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 dut mutant YH Information about the mutated molecule: FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). NCBIGene: 1167368 The gene dut from the strain Brucella suis 1330 is a virulence gene. PMID: 12438693 UniProtKB accession: P64005 A mutant of strain Brucella suis 1330 that lacks an intact gene dut. B. suis 1330 ansC mutant PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene ansC. YH NCBIGene: 1167369 The gene ansC from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: Q8FZ27 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. suis 1330 purE mutant UniProtKB accession: Q8FYW3 The gene purE from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene purE. YH Information about the mutated molecule: FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3). CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3). PATHWAY: Nucleotide biosynthesis NCBIGene: 1167437 PMID: IMP biosynthesis B. suis 1330 pyc mutant The gene pyc from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1167474 UniProtKB accession: Q8FYT0 PMID: 10678941 A mutant of strain Brucella suis 1330 that lacks an intact gene pyc. Information about the mutated molecule: MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. YH B. suis 1330 livH mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1167484 PMID: 14979322 The gene livH from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene livH. UniProtKB accession: Q8FYS1 B. suis 1330 purH mutant UniProtKB accession: P67540 NCBIGene: 1167509 Information about the mutated molecule: CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis YH The gene purH from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene purH. PMID: IMP biosynthesis B. suis 1330 leuC mutant UniProtKB accession: Q8FYG9 A mutant of strain Brucella suis 1330 that lacks an intact gene leuC. PMID: L-leucine biosynthesis Information about the mutated molecule: FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis NCBIGene: 1167606 The gene leuC from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 rplS mutant Information about the mutated molecule: FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. The gene rplS from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: P66079 NCBIGene: 1167607 PMID: 15271960 A mutant of strain Brucella suis 1330 that lacks an intact gene rplS. YH B. suis 1330 omp19 mutant NCBIGene: 1167630 Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane The gene omp19 from the strain Brucella suis 1330 is a virulence gene. UniProtKB accession: P0A3P2 YH A mutant of strain Brucella suis 1330 that lacks an intact gene omp19. PMID: lipid-anchor(Swiss-Prot: P0A3P2). MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2). SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2). MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. B. suis 1330 lysA mutant The gene lysA from the strain Brucella suis 1330 is a virulence gene. YH UniProtKB accession: Q8FYA2 A mutant of strain Brucella suis 1330 that lacks an intact gene lysA. NCBIGene: 1167684 Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. PMID: 12438693 B. suis 1330 hpt mutant The gene hpt from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1167686 YH Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB accession: Q8FYA0 A mutant of strain Brucella suis 1330 that lacks an intact gene hpt. B. suis 1330 hisC mutant YH NCBIGene: 1167688 The gene hisC from the strain Brucella suis 1330 is a virulence gene. Information about the mutated molecule: CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella suis 1330 that lacks an intact gene hisC. UniProtKB accession: Q8FY98 PMID: L-histidine biosynthesis B. suis 1330 hisF mutant Information about the mutated molecule: FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis YH NCBIGene: 1167788 The gene hisF from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene hisF. PMID: L-histidine biosynthesis UniProtKB accession: Q8FY07 B. suis 1330 bvrR mutant PMID: 12218183 UniProtKB accession: Q8FY04 YH Information about the mutated molecule: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. A mutant of strain Brucella suis 1330 that lacks an intact gene bvrR. NCBIGene: 1167793 The gene bvrR from the strain Brucella suis 1330 is a virulence gene. B. suis 1330 bvrS mutant NCBIGene: 1167794 PMID: 12218183 UniProtKB accession: Q8FY03 Information about the mutated molecule: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. A mutant of strain Brucella suis 1330 that lacks an intact gene bvrS. The gene bvrS from the strain Brucella suis 1330 is a virulence gene. YH B. suis 1330 dnaK mutant YH A mutant of strain Brucella suis 1330 that lacks an intact gene dnaK. Information about the mutated molecule: FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2). INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2). SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2). MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. UniProtKB accession: Q8FXX2 PMID: 11854256 The gene dnaK from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1167828 B. suis 1330 pmtA mutant The gene pmtA from the strain Brucella suis 1330 is a virulence gene. A mutant of strain Brucella suis 1330 that lacks an intact gene pmtA. YH NCBIGene: 1167830 UniProtKB accession: Q8FXX0 Information about the mutated molecule: MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. PMID: 16882035 B. suis 1330 mutM mutant PMID: 14979322 A mutant of strain Brucella suis 1330 that lacks an intact gene mutM. The gene mutM from the strain Brucella suis 1330 is a virulence gene. NCBIGene: 1167886 Information about the mutated molecule: FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6). SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6). SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6). SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6). MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8FXR6 YH B. melitensis 16M hpt mutant Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene hpt. NCBIGene: 1195794 PMID: 14979322 UniProtKB accession: Q8YJK1 The gene hpt from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. melitensis 16M lysA mutant PMID: 12438693 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lysA. NCBIGene: 1195796 The gene lysA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YJJ9 Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. B. melitensis 16M BMEI0085 mutant UniProtKB accession: Q8YJJ8 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI0085. Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. The gene BMEI0085 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 14979322 NCBIGene: 1195797 B. melitensis 16M omp19 mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene omp19. YH Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane UniProtKB accession: P0A3P1 NCBIGene: 1195847 The gene omp19 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: lipid-anchor(Swiss-Prot: P0A3P2). MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2). SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2). MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. B. melitensis 16M rplS mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene rplS. NCBIGene: 1195868 PMID: 15271960 The gene rplS from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH Information about the mutated molecule: FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. UniProtKB accession: P66078 B. melitensis 16M leuC mutant PMID: L-leucine biosynthesis The gene leuC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH NCBIGene: 1195869 Information about the mutated molecule: FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis UniProtKB accession: Q8YJC9 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene leuC. B. melitensis 16M gntR4 mutant UniProtKB accession: Q8YJB7 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR4. The gene gntR4 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. PMID: 16113274 NCBIGene: 1195881 YH B. melitensis 16M pstP mutant The gene pstP from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Phosphoenolypruvate phosphotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 UniProtKB accession: Q8YJ96 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pstP. NCBIGene: 1195902 B. melitensis 16M purH mutant Information about the mutated molecule: CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis PMID: IMP biosynthesis A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purH. YH The gene purH from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1195945 UniProtKB accession: P67539 B. melitensis 16M livH mutant YH NCBIGene: 1195970 PMID: 14979322 UniProtKB accession: Q8YJ28 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene livH. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. The gene livH from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M pyc mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pyc. NCBIGene: 1195978 The gene pyc from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YJ20 Information about the mutated molecule: MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. PMID: 10678941 B. melitensis 16M mosC mutant The gene mosC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Rhizopine transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene mosC. UniProtKB accession: Q8YJ19 PMID: 14979322 NCBIGene: 1195979 B. melitensis 16M mgps mutant PMID: 14979322 NCBIGene: 1195987 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene mgps. The gene mgps from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: RNA helicase family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YJ11 YH B. melitensis 16M purE mutant PMID: IMP biosynthesis YH Information about the mutated molecule: FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3). CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3). PATHWAY: Nucleotide biosynthesis The gene purE from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196007 UniProtKB accession: P52558 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purE. B. melitensis 16M gntR2 mutant YH PMID: 16113274 UniProtKB accession: Q8YIY4 NCBIGene: 1196016 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR2. Information about the mutated molecule: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. The gene gntR2 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M gntR17 mutant PMID: 16113274 NCBIGene: 1196031 Information about the mutated molecule: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. YH UniProtKB accession: Q8YIW9 The gene gntR17 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR17. B. melitensis 16M ansC mutant PMID: 14979322 YH UniProtKB accession: Q8YIT5 The gene ansC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ansC. NCBIGene: 1196068 B. melitensis 16M dut mutant UniProtKB accession: P64004 The gene dut from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 12438693 Information about the mutated molecule: FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). NCBIGene: 1196069 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dut. YH B. melitensis 16M macA mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene macA. NCBIGene: 1196070 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 UniProtKB accession: Q8YIT3 The gene macA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M alkA mutant NCBIGene: 1196093 YH UniProtKB accession: Q8YIR1 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene alkA. PMID: 14979322 The gene alkA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M dsbB mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YIQ9 PMID: 14979322 The gene dsbB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dsbB. NCBIGene: 1196095 B. melitensis 16M arsR6 mutant UniProtKB accession: Q8YIL4 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene arsR6. Information about the mutated molecule: FUNCTIONAL GROUP: ArsR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. YH NCBIGene: 1196141 PMID: 16113274 The gene arsR6 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M dppA mutant NCBIGene: 1196144 YH PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dppA. UniProtKB accession: Q8YIL1 The gene dppA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M leuA mutant PMID: L-leucine biosynthesis UniProtKB accession: Q8YIJ3 Information about the mutated molecule: FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene leuA. NCBIGene: 1196162 The gene leuA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. melitensis 16M BMEI0455 mutant UniProtKB accession: Q8YII9 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI0455. The gene BMEI0455 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH NCBIGene: 1196166 PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Glutathione S-transferase, C-terminal domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M pth mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pth. The gene pth from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196191 YH PMID: 15385478 Information about the mutated molecule: FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. UniProtKB accession: P65863 B. melitensis 16M lpsB mutant NCBIGene: 1196220 PMID: 14979322 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lpsB. The gene lpsB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YID5 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: Core synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M trkH mutant NCBIGene: 1196223 PMID: 14979322 The gene trkH from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene trkH. UniProtKB accession: Q8YID2 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Thioredoxin reductase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. B. melitensis 16M lysR mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YID1 The gene lysR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lysR. NCBIGene: 1196224 YH PMID: 14979322 B. melitensis 16M aspC mutant Information about the mutated molecule: MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. UniProtKB accession: Q8YIC8 The gene aspC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 12761078 NCBIGene: 1196227 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene aspC. B. melitensis 16M carAB mutant UniProtKB accession: Q8YIB8 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Clut. and pyr. Syntheis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene carAB. NCBIGene: 1196237 PMID: 14979322 The gene carAB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M pncA mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pncA. Information about the mutated molecule: MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. YH NCBIGene: 1196256 PMID: 12761078, 15135535 The gene pncA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YIA0 B. melitensis 16M bicA mutant UniProtKB accession: Q8YI40 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene bicA. The gene bicA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH NCBIGene: 1196316 B. melitensis 16M serB mutant YH UniProtKB accession: Q8YI30 NCBIGene: 1196326 Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. The gene serB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 12438693 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene serB. B. melitensis 16M miaA mutant NCBIGene: 1196327 UniProtKB accession: Q8YI29 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene miaA. PMID: 12438693 YH Information about the mutated molecule: FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. The gene miaA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M ilvI mutant The gene ilvI from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196328 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Val. Leu., Isoleu. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ilvI. PMID: 14979322 UniProtKB accession: Q8YI28 B. melitensis 16M ilvC mutant UniProtKB accession: Q8YI21 YH Information about the mutated molecule: CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). PATHWAY: Amino-acid biosynthesis NCBIGene: 1196335 PMID: L-isoleucine biosynthesis A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ilvC. The gene ilvC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M aspB mutant UniProtKB accession: Q8YI19 PMID: 14979322 YH The gene aspB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene aspB. NCBIGene: 1196337 B. melitensis 16M BMEI0671 mutant YH NCBIGene: 1196382 PMID: 14979322 The gene BMEI0671 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Terc dome (efflux) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI0671. UniProtKB accession: Q8YHX5 B. melitensis 16M cobB mutant NCBIGene: 1196416 PMID: 14638795 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cobB. UniProtKB accession: Q8YHU1 Information about the mutated molecule: FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020). PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020). SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020). MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. The gene cobB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. melitensis 16M thrA mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene thrA. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1196436 UniProtKB accession: Q8YHS1 The gene thrA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 14979322 B. melitensis 16M gloA mutant YH UniProtKB accession: Q8YHR6 PMID: 14979322 NCBIGene: 1196441 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gloA. The gene gloA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. B. melitensis 16M rpoA mutant PMID: 14638795 Information about the mutated molecule: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene rpoA. NCBIGene: 1196492 YH The gene rpoA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YHL6 B. melitensis 16M recA mutant The gene recA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 8321120 NCBIGene: 1196498 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene recA. UniProtKB accession: P65975 Information about the mutated molecule: FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993]. B. melitensis 16M uppS mutant YH Information about the mutated molecule: FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9). CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9). COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9). SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1196538 UniProtKB accession: Q8YHH3 PMID: 12438693 The gene uppS from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene uppS. B. melitensis 16M ppiD mutant NCBIGene: 1196556 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ppiD. PMID: 14979322 YH UniProtKB accession: Q8YHF6 Information about the mutated molecule: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004]. FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene ppiD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M ntrY mutant UniProtKB accession: Q8YHD4 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ntrY. The gene ntrY from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. PMID: 10678941 NCBIGene: 1196578 YH B. melitensis 16M hfq mutant Information about the mutated molecule: FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. The gene hfq from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: P0A3G7 PMID: 14521880, 12730323 NCBIGene: 1196583 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene hfq. YH B. melitensis 16M lon mutant The gene lon from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196587 YH PMID: 10672180 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lon. UniProtKB accession: Q8YHC6 Information about the mutated molecule: FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7). CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7). SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7). SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7). MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. B. melitensis 16M uvrA mutant YH NCBIGene: 1196589 The gene uvrA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene uvrA. Information about the mutated molecule: FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. UniProtKB accession: Q8YHC4 PMID: 16816190 B. melitensis gntR5 hpt mutant Information about the mutated molecule: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR5. The gene gntR5 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YHC1 PMID: 16113274 NCBIGene: 1196592 YH B. melitensis 16M caiB mutant NCBIGene: 1196609 UniProtKB accession: Q8YHA4 YH Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene caiB. The gene caiB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M cysK mutant PMID: 14979322 The gene cysK from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YH71 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cysK. YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1196644 B. melitensis 16M glnA mutant Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1196690 UniProtKB accession: Q8YH25 YH The gene glnA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 12438693 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene glnA. B. melitensis 16M wbdA mutant YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene wbdA. PMID: 14979322 UniProtKB accession: Q8YH07 The gene wbdA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196708 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M moaA mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1196730 The gene moaA NOT caiB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YGY6 PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene moaA NOT caiB. B. melitensis 16M dsbA mutant The gene dsbA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dsbA. UniProtKB accession: Q8YGW5 NCBIGene: 1196751 B. melitensis 16M nifS mutant Information about the mutated molecule: FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004]. FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. The gene nifS from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene nifS. UniProtKB accession: Q8YGW2 NCBIGene: 1196754 PMID: 14979322 YH B. melitensis 16M amiC mutant UniProtKB accession: Q8YGV1 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene amiC. YH PMID: 14979322 NCBIGene: 1196767 The gene amiC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M dsbA mutant NCBIGene: 1196771 The gene dsbA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YGU7 YH PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dsbA. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M tig mutant YH UniProtKB accession: Q8YGT8 Information about the mutated molecule: FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene tig. PMID: 14638795 The gene tig from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196780 B. melitensis 16M artI mutant PMID: 14979322 NCBIGene: 1196815 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene artI. The gene artI from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YGQ4 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. B. melitensis 16M cbbE mutant YH PMID: 14979322 UniProtKB accession: Q8YGP2 The gene cbbE from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1196827 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribulose-phosphate 3-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cbbE. B. melitensis 16M purL mutant NCBIGene: 1196838 Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183). PATHWAY: Nucleotide biosynthesis The gene purL from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: IMP biosynthesis A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purL. UniProtKB accession: Q8YGN1 YH B. melitensis 16M glyA mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene glyA. UniProtKB accession: Q8YGG7 The gene glyA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 12438693 Information about the mutated molecule: FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1196903 B. melitensis 16M BMEI1229 mutant The gene BMEI1229 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Exonuclease X-T domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1229. YH NCBIGene: 1196940 UniProtKB accession: Q8YGD0 PMID: 14979322 B. melitensis 16M galE mutant YH The gene galE from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 NCBIGene: 1196948 UniProtKB accession: Q8YGC2 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene galE. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M purM mutant NCBIGene: 1196951 The gene purM from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis UniProtKB accession: Q8YGB9 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purM. PMID: IMP biosynthesis B. melitensis 16M purN mutant The gene purN from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YGB8 PMID: 12761078 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purN. NCBIGene: 1196952 Information about the mutated molecule: MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. YH B. melitensis 16M omp25 mutant Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689). SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689). MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene omp25. PMID: 11447156 NCBIGene: 1196960 UniProtKB accession: Q45321 YH The gene omp25 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M BMEI1258 mutant The gene BMEI1258 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1258. PMID: 14979322 YH NCBIGene: 1196969 UniProtKB accession: Q8YGA2 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. B. melitensis 16M pyrC mutant The gene pyrC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH NCBIGene: 1196992 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pyrC. PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YG80 B. melitensis 16M spotT mutant The gene spotT from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YG65 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene spotT. PMID: 14979322 YH Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197007 B. melitensis 16M lpsA mutant UniProtKB accession: Q8YG36 YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lpsA. NCBIGene: 1197037 The gene lpsA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M htrA mutant Information about the mutated molecule: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002]. FUNCTION: Protease [Ref412:Kohler et al., 2002]. MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. The gene htrA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197041 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene htrA. PMID: 12438693 YH UniProtKB accession: Q8YG32 B. melitensis 16M feuQ mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197047 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene feuQ. YH UniProtKB accession: Q8YG26 PMID: 14979322 The gene feuQ from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M feuP mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene feuP. YH PMID: 14979322 NCBIGene: 1197048 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q7CNU2 The gene feuP from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M BMEI1339 mutant UniProtKB accession: Q8YG23 YH NCBIGene: 1197050 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Agrobacterium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene BMEI1339 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1339. B. melitensis 16M BMEI1361 mutant PMID: 14979322 YH The gene BMEI1361 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197072 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1361. UniProtKB accession: Q8YG01 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. B. melitensis 16M wbpZ mutant The gene wbpZ from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197104 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene wbpZ. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YFW9 YH PMID: 14979322 B. melitensis 16M pmm mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YFW6 NCBIGene: 1197107 The gene pmm from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pmm. B. melitensis 16M wbkA mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene wbkA. The gene wbkA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YFV9 PMID: 14979322 NCBIGene: 1197115 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. B. melitensis 16M rfbD mutant The gene rfbD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197124 UniProtKB accession: F8WJX8 PMID: 14979322 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene rfbD. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M perA mutant UniProtKB accession: Q8YFV3 The gene perA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene perA. YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1197125 B. melitensis 16M wbpL mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH The gene wbpL from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YFU4 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene wbpL. NCBIGene: 1197137 B. melitensis 16M dsbA mutant PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dsbA. NCBIGene: 1197151 UniProtKB accession: Q8YFT0 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH The gene dsbA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M BMEI1443 mutant Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197154 UniProtKB accession: Q8YFS7 YH The gene BMEI1443 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1443. PMID: 14979322 B. melitensis 16M BMEI1448 mutant YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1448. UniProtKB accession: Q8YFS2 NCBIGene: 1197159 PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: EAL domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene BMEI1448 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M thrC mutant NCBIGene: 1197161 YH UniProtKB accession: Q8YFS0 The gene thrC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene thrC. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M tldD mutant NCBIGene: 1197179 The gene tldD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene tldD. UniProtKB accession: Q8YFQ2 B. melitensis 16M purF mutant The gene purF from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 12761078 NCBIGene: 1197199 Information about the mutated molecule: MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. UniProtKB accession: Q8YFN2 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purF. B. melitensis 16M dxps mutant The gene dxps from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197209 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dxps. PMID: 14979322 YH UniProtKB accession: Q8YFM2 Information about the mutated molecule: FUNCTIONAL GROUP: Vitamines cofactors [Ref6462:Delrue et al., 2004]. FUNCTION: Thiamine synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. B. melitensis 16M aroC mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene aroC. NCBIGene: 1197217 Information about the mutated molecule: CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis PMID: chorismate biosynthesis The gene aroC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: P63607 YH B. melitensis 16M purD mutant The gene purD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: IMP biosynthesis UniProtKB accession: Q8YFK1 YH NCBIGene: 1197230 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene purD. Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis B. melitensis 16M BMEI1531 mutant The gene BMEI1531 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1531. YH PMID: 14979322 UniProtKB accession: Q8YFI9 Information about the mutated molecule: FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: protein-protein interaction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197242 B. melitensis 16M bacA mutant NCBIGene: 1197264 PMID: 10741969, 12270820 Information about the mutated molecule: MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6533:Ferguson et al., 2002]. YH The gene bacA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene bacA. UniProtKB accession: Q8YFG9 B. melitensis 16M lysR18 mutant Information about the mutated molecule: FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lysR18. NCBIGene: 1197284 UniProtKB accession: Q8YFE9 The gene lysR18 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 16113274 YH B. melitensis 16M vsrB mutant UniProtKB accession: Q8YFB6 PMID: 14979322 NCBIGene: 1197317 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene vsrB. The gene vsrB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. melitensis 16M pyrD mutant YH Information about the mutated molecule: MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pyrD. PMID: 12761078 NCBIGene: 1197322 The gene pyrD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YFB1 B. melitensis 16M pgi mutant UniProtKB accession: Q8YF86 YH PMID: glycolysis Information about the mutated molecule: CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pgi. The gene pgi from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197347 B. melitensis 16M BMEI1658 mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. The gene BMEI1658 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 NCBIGene: 1197369 UniProtKB accession: Q8YF67 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1658. B. melitensis 16M hisD mutant NCBIGene: 1197379 Information about the mutated molecule: FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis The gene hisD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: L-histidine biosynthesis A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene hisD. UniProtKB accession: Q8YF59 YH B. melitensis 16M malK mutant Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. The gene malK from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene malK. YH UniProtKB accession: Q8YF14 PMID: 14979322 NCBIGene: 1197424 B. melitensis 16M exsA mutant PMID: 14979322 NCBIGene: 1197453 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene exsA. UniProtKB accession: Q8YEY5 The gene exsA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. YH B. melitensis 16M metH mutant The gene metH from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YEW8 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene metH. YH NCBIGene: 1197470 B. melitensis 16M cysI mutant YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cysI. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. The gene cysI from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 NCBIGene: 1197477 UniProtKB accession: Q8YEW1 B. melitensis 16M glnL mutant YH The gene glnL from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YEU1 PMID: 14979322 NCBIGene: 1197497 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene glnL. Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Nitrogen regulatory IIA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M glnD mutant Information about the mutated molecule: FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312). CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312). SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312). MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. UniProtKB accession: Q8YES3 PMID: 10678941 The gene glnD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene glnD. NCBIGene: 1197515 YH B. melitensis 16M BMEI1809 mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1809. PMID: 14979322 The gene BMEI1809 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197520 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: ERFK/YBIS/YCFS/YNHG family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YER8 YH B. melitensis 16M ndvB mutant UniProtKB accession: Q8YEP1 The gene ndvB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ndvB. NCBIGene: 1197548 B. melitensis 16M BMEI1844 mutant Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Domain of Unkown Function (DUF930) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH UniProtKB accession: Q8YEN4 The gene BMEI1844 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1844. NCBIGene: 1197555 B. melitensis 16M ilvD mutant Information about the mutated molecule: CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis YH PMID: L-isoleucine biosynthesis A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ilvD. NCBIGene: 1197559 The gene ilvD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YEN0 B. melitensis 16M cysY mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide oxidoreducate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YEM9 The gene cysY from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cysY. NCBIGene: 1197560 B. melitensis 16M BMEI1859 mutant The gene BMEI1859 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197570 UniProtKB accession: Q8YEL9 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Uncharacterised protein family 0005 [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1859. PMID: 14979322 YH B. melitensis 16M BMEI1879 mutant UniProtKB accession: Q8YEJ9 PMID: 14979322 The gene BMEI1879 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1879. NCBIGene: 1197590 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH B. melitensis 16M pgm mutant Information about the mutated molecule: MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6534:Ko and Splitter, 2003]. NCBIGene: 1197597 YH The gene pgm from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pgm. UniProtKB accession: Q8YEJ2 PMID: 10992476, 12525425 B. melitensis 16M BMEI1902 mutant Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 NCBIGene: 1197613 The gene BMEI1902 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YEH6 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEI1902. B. melitensis 16M lysR13 mutant YH PMID: 16113274 Information about the mutated molecule: FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. UniProtKB accession: Q8YEG5 The gene lysR13 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lysR13. NCBIGene: 1197624 B. melitensis 16M rpsA mutant UniProtKB accession: Q8YEG3 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene rpsA. PMID: 10678941 Information about the mutated molecule: MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. The gene rpsA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197626 YH B. melitensis 16M mutM mutant NCBIGene: 1197657 PMID: 14979322 YH Information about the mutated molecule: FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6). SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6). SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6). SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6). MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene mutM. UniProtKB accession: Q8YED2 The gene mutM from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M dnaK mutant UniProtKB accession: Q8YE76 YH NCBIGene: 1197713 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dnaK. The gene dnaK from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 11854256 Information about the mutated molecule: FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2). INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2). SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2). MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. B. melitensis 16M bvrS mutant Information about the mutated molecule: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. UniProtKB accession: Q8YE43 PMID: 16077108, 12414153, 9826346, 11401996, 12414149, 12218183 YH The gene bvrS from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene bvrS. NCBIGene: 1197746 B. melitensis 16M bvrR mutant UniProtKB accession: Q8YE42 PMID: 16077108, 12414153, 9826346, 11401996, 12414149, 12218183 NCBIGene: 1197747 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene bvrR. Information about the mutated molecule: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. The gene bvrR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M hisF mutant PMID: L-histidine biosynthesis YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene hisF. UniProtKB accession: Q8YE37 Information about the mutated molecule: FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis NCBIGene: 1197752 The gene hisF from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M omp10 mutant The gene omp10 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane UniProtKB accession: P0A3N8 PMID: lipid-anchor(Swiss-Prot: P0A3N9). MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9). SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9). MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene omp10. YH NCBIGene: 1197788 B. melitensis 16M hemH mutant NCBIGene: 1197789 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene hemH. PMID: last step(Swiss-Prot: P0A3D7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7). SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7). MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. Information about the mutated molecule: FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis UniProtKB accession: P0A3D6 The gene hemH from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. melitensis 16M virb1 mutant UniProtKB accession: Q8YDZ5 PMID: 15322008, 10940027, 16113325, 16272371 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virb1. NCBIGene: 1197796 The gene virb1 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH Information about the mutated molecule: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6539:den et al., 2004]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6540:Sieira et al., 2000]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. B. melitensis 16M virB2 mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virB2. UniProtKB accession: Q9RPY3 Information about the mutated molecule: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. YH PMID: 15322008, 16113325 The gene virB2 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197797 B. melitensis 16M virB3 mutant YH PMID: 12761078 The gene virB3 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virB3. UniProtKB accession: Q9RPY2 NCBIGene: 1197798 B. melitensis 16M virb4 mutant The gene virb4 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197799 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virb4. UniProtKB accession: Q8YDZ4 Information about the mutated molecule: MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6541:Watarai et al., 2002]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6542:Kim et al., 2005]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. PMID: 11988518, 15869716, 15135535 YH B. melitensis 16M virB5 mutant NCBIGene: 1197800 The gene virB5 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virB5. UniProtKB accession: Q8YDZ3 Information about the mutated molecule: MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. YH PMID: 12595417, 12595466, 16113325, 10510235 B. melitensis 16M virb6 mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virb6. UniProtKB accession: Q8YDZ2 Information about the mutated molecule: MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. NCBIGene: 1197801 The gene virb6 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. melitensis 16M virB8 mutant PMID: 10678941, 12414149 NCBIGene: 1197803 Information about the mutated molecule: MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virB8. YH UniProtKB accession: Q9RPX7 The gene virB8 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M virb9 mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virb9. PMID: 11349069, 10510235, 11437834, 12414149 YH NCBIGene: 1197804 The gene virb9 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6545:Rittig et al., 2001]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6546:Delrue et al., 2001]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. UniProtKB accession: Q8YDZ1 B. melitensis 16M virb10 mutant YH Information about the mutated molecule: MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6540:Sieira et al., 2000]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6547:Celli et al., 2003]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6463:Hong et al., 2000]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6538:Briones et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6548:Boschiroli et al., 2002]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. PMID: 10940027, 12925673, 10858227, 11401996, 12414154, 11260139 NCBIGene: 1197805 UniProtKB accession: Q8YDZ0 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virb10. The gene virb10 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M virb11 mutant The gene virb11 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene virb11. Information about the mutated molecule: MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. NCBIGene: 1197806 UniProtKB accession: Q8YDY9 PMID: 15312849 YH B. melitensis 16M gltD mutant PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gltD. NCBIGene: 1197810 The gene gltD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YDY5 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Glut. sunthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. YH B. melitensis 16M BMEII0040 mutant UniProtKB accession: Q8YDY4 The gene BMEII0040 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197811 YH PMID: 10858227 Information about the mutated molecule: MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0040. B. melitensis 16M nodV mutant The gene nodV from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene nodV. Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 NCBIGene: 1197823 UniProtKB accession: Q8YDX2 B. melitensis 16M mgtB mutant YH Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197827 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene mgtB. PMID: 14979322 The gene mgtB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YDW8 B. melitensis 16M dhbC mutant The gene dhbC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dhbC. NCBIGene: 1197848 UniProtKB accession: Q8YDU7 Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Sideophore sysnhesis, Fe3+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH B. melitensis 16M rbsK mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene rbsK. PMID: 14979322 The gene rbsK from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1197860 UniProtKB accession: Q8YDT6 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M gntR10 mutant UniProtKB accession: Q8YDQ9 Information about the mutated molecule: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. The gene gntR10 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 16113274 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR10. NCBIGene: 1197887 YH B. melitensis 16M BMEII0128 mutant PMID: 14979322 NCBIGene: 1197899 The gene BMEII0128 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Uncharacterised protein family (DUF0261) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0128. UniProtKB accession: Q8YDP7 B. melitensis 16M pheB mutant Information about the mutated molecule: FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: Dioxygenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1197907 PMID: 14979322 The gene pheB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YDN9 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pheB. B. melitensis 16M fliC mutant UniProtKB accession: Q8YDM5 YH NCBIGene: 1197921 PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene fliC. The gene fliC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellin [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M fliF mutant UniProtKB accession: Q8YDM4 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene fliF. Information about the mutated molecule: FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane PMID: multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3). SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3). MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. NCBIGene: 1197922 The gene fliF from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M motB mutant PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene motB. The gene motB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH UniProtKB accession: Q8YDM1 NCBIGene: 1197925 B. melitensis 16M ftcR mutant PMID: 17056750 NCBIGene: 1197929 The gene ftcR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ftcR. Information about the mutated molecule: MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria [Ref6549:Léonard et al., 2007]. UniProtKB accession: Q8YDL7 B. melitensis 16M flgE mutant YH PMID: 14979322 UniProtKB accession: Q8YDL6 NCBIGene: 1197930 The gene flgE from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene flgE. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M flghA mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Export apparatus [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene flghA. UniProtKB accession: Q8YDK9 NCBIGene: 1197937 The gene flghA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 B. melitensis 16M znuC mutant UniProtKB accession: Q8YDJ8 The gene znuC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene znuC. Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197948 YH PMID: 14979322 B. melitensis 16M znuA mutant YH UniProtKB accession: Q8YDJ7 Information about the mutated molecule: MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6550:Kim et al., 2004]. NCBIGene: 1197949 The gene znuA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene znuA. PMID: 12761078, 15472468 B. melitensis 16M BMEII0274 mutant NCBIGene: 1198045 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0274. UniProtKB accession: P64066 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: GTPase of unknown function domain, FeoB domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 The gene BMEII0274 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M dbsA mutant PMID: 14979322 The gene dbsA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1198072 UniProtKB accession: Q8YD77 YH Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Ribose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dbsA. B. melitensis 16M cobW mutant Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. The gene cobW from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YD69 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cobW. PMID: 12438693 NCBIGene: 1198080 B. melitensis 16M BMEII0318 mutant UniProtKB accession: Q8YD59 NCBIGene: 1198090 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0318. YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene BMEII0318 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M BMEII0336 mutant YH The gene BMEII0336 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0336. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198108 PMID: 14979322 UniProtKB accession: Q8YD41 B. melitensis 16M dacF mutant PMID: 14979322 The gene dacF from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene dacF. NCBIGene: 1198122 UniProtKB accession: Q8YD27 YH B. melitensis 16M araG mutant PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene araG. UniProtKB accession: Q8YD16 NCBIGene: 1198133 YH The gene araG from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. B. melitensis 16M fdhA mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene fdhA. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YCZ9 PMID: 14979322 YH The gene fdhA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1198150 B. melitensis 16M lysR12 mutant NCBIGene: 1198162 YH Information about the mutated molecule: FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. The gene lysR12 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene lysR12. PMID: 16113274 UniProtKB accession: Q8YCY7 B. melitensis 16M eryC mutant Information about the mutated molecule: MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6551:Burkhardt et al., 2005]. The gene eryC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene eryC. YH NCBIGene: 1198200 UniProtKB accession: Q8YCV0 PMID: 10708387, 16177356 B. melitensis 16M eryB mutant PMID: 10708387, 16177356 UniProtKB accession: Q8YCU9 YH The gene eryB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6551:Burkhardt et al., 2005]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene eryB. NCBIGene: 1198201 B. melitensis 16M gntR1 mutant NCBIGene: 1198247 PMID: 16113274 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR1. The gene gntR1 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. UniProtKB accession: Q8YCQ3 YH B. melitensis 16M galcD mutant The gene galcD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene galcD. PMID: 14979322 NCBIGene: 1198257 UniProtKB accession: Q8YCP3 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH B. melitensis 16M nikA mutant PMID: 14979322 NCBIGene: 1198259 UniProtKB accession: Q8YCP1 YH Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. The gene nikA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene nikA. B. melitensis 16M zwf mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene zwf. The gene zwf from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YCL5 PMID: 12761078 NCBIGene: 1198285 Information about the mutated molecule: MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. B. melitensis 16M xseA mutant UniProtKB accession: Q8YCK1 YH Information about the mutated molecule: FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. NCBIGene: 1198299 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene xseA. The gene xseA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14638795 B. melitensis 16M mocC mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Rhizopine/inositol catabolism [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198342 The gene mocC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YCG0 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene mocC. B. melitensis 16M RpiR mutant PMID: 14979322 NCBIGene: 1198345 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene RpiR. Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH The gene RpiR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YCF7 B. melitensis 16M sodC mutant UniProtKB accession: P66826 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene sodC. PMID: 10816475 YH NCBIGene: 1198353 Information about the mutated molecule: FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. The gene sodC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M fbpA mutant The gene fbpA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1198356 PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene fbpA. UniProtKB accession: Q8YCE7 B. melitensis 16M BMEII0591 mutant The gene BMEII0591 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14638795 YH UniProtKB accession: Q8YCE1 Information about the mutated molecule: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0591. NCBIGene: 1198363 B. melitensis 16M ugpA mutant UniProtKB accession: D0B782 YH NCBIGene: 1198396 The gene ugpA from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. PMID: 14638795 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ugpA. B. melitensis 16M BMEII0626 mutant NCBIGene: 1198398 UniProtKB accession: Q8YCA6 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0626. The gene BMEII0626 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptidase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 YH B. melitensis 16M divK mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. The gene divK from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 NCBIGene: 1198431 UniProtKB accession: Q8YC73 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene divK. B. melitensis 16M pyrC mutant UniProtKB accession: Q8YC63 PMID: 14979322 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pyrC. Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH NCBIGene: 1198441 The gene pyrC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M pyrB mutant YH The gene pyrB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene pyrB. Information about the mutated molecule: CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis UniProtKB accession: P65611 PMID: UMP biosynthesis NCBIGene: 1198442 B. melitensis 16M aidB mutant YH NCBIGene: 1198443 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene aidB. UniProtKB accession: Q8YC61 The gene aidB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 B. melitensis 16M rbsC mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 The gene rbsC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1198473 UniProtKB accession: Q8YC31 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene rbsC. YH B. melitensis 16M cydB mutant PMID: 11274104, 12761078 The gene cydB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YBX7 NCBIGene: 1198531 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cydB. YH Information about the mutated molecule: MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. B. melitensis 16M cydC mutant PMID: 14979322 NCBIGene: 1198533 The gene cydC from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YBX5 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cydC. Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH B. melitensis 16M cydD mutant The gene cydD from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. UniProtKB accession: Q8YBX4 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene cydD. NCBIGene: 1198534 Information about the mutated molecule: MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. YH PMID: 12761078 B. melitensis 16M ssuB mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Permease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YBT7 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene ssuB. PMID: 14979322 YH The gene ssuB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1198571 B. melitensis 16M glpK mutant The gene glpK from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene glpK. YH PMID: first (rate-limiting) step(Swiss-Prot: Q8FWK8). SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8). MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Information about the mutated molecule: FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8). CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8). PATHWAY: Glycerol utilization NCBIGene: 1198595 UniProtKB accession: Q8YBR2 B. melitensis 16M xfp mutant UniProtKB accession: Q8YBL8 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene xfp. NCBIGene: 1198653 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. The gene xfp from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 YH B. melitensis 16M manB mutant The gene manB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 NCBIGene: 1198671 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YBK1 YH A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene manB. B. melitensis 16M wbpW mutant UniProtKB accession: Q8YBK0 PMID: 14979322 YH NCBIGene: 1198672 The gene wbpW from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene wbpW. B. melitensis 16M BMEII0923 mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0923. YH The gene BMEII0923 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YBH7 PMID: 14979322 NCBIGene: 1198695 B. melitensis 16M nrdI mutant Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages [Ref6462:Delrue et al., 2004]. YH The gene nrdI from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene nrdI. UniProtKB accession: P65546 NCBIGene: 1198703 PMID: 14979322 B. melitensis 16M nrdH mutant PMID: 14979322 UniProtKB accession: Q8YBG8 The gene nrdH from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene nrdH. NCBIGene: 1198704 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. YH B. melitensis 16M BMEII0935 mutant Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Bacterial protein of unknown function (DUF89) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH NCBIGene: 1198707 UniProtKB accession: Q8YBG5 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII0935. PMID: 14979322 The gene BMEII0935 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M narG mutant NCBIGene: 1198722 UniProtKB accession: Q8YBF0 The gene narG from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. Information about the mutated molecule: MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene narG. PMID: 12438693 YH B. melitensis 16M norE mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene norE. NCBIGene: 1198773 PMID: 14979322 The gene norE from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH UniProtKB accession: Q8YB99 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M BMEII1037 mutant PMID: 14979322 The gene BMEII1037 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH NCBIGene: 1198809 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII1037. Information about the mutated molecule: FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: Zinc protease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YB63 B. melitensis 16M BMEII1045 mutant UniProtKB accession: Q8YB55 YH The gene BMEII1045 from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 NCBIGene: 1198817 Information about the mutated molecule: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene BMEII1045. B. melitensis 16M gluP mutant PMID: multi-pass membrane protein (Probable)(Swiss-Prot: Q8YB48). SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(Swiss-Prot: Q8YB48). MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse [Ref6474:Essenberg et al., 2002]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gluP. UniProtKB accession: Q8YB48 Information about the mutated molecule: FUNCTION: Intake of glucose and galactose (Potential)(Swiss-Prot: Q8YB48). SUBCELLULAR LOCATION: Inner membrane The gene gluP from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. NCBIGene: 1198825 YH B. melitensis 16M gntR mutant PMID: 14979322 NCBIGene: 1198838 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gntR. UniProtKB accession: Q8YB35 The gene gntR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. melitensis 16M flgI mutant NCBIGene: 1198856 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene flgI. Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: P-ring [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. YH PMID: 14979322 UniProtKB accession: Q8YB17 The gene flgI from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M deoR mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene deoR. NCBIGene: 1198865 UniProtKB accession: Q8YB08 YH PMID: 14979322 The gene deoR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. B. melitensis 16M gtrB mutant UniProtKB accession: Q8YB00 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gtrB. NCBIGene: 1198873 The gene gtrB from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH PMID: 14979322 B. melitensis 16M vjbR mutant Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q8YAY5 A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene vjbR. NCBIGene: 1198888 The gene vjbR from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. PMID: 14979322 YH B. melitensis 16M gnd mutant A mutant of strain Brucella melitensis bv. 1 str. 16M that lacks an intact gene gnd. Information about the mutated molecule: MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. UniProtKB accession: Q8YAX7 PMID: 12761078 NCBIGene: 1198896 The gene gnd from the strain Brucella melitensis bv. 1 str. 16M is a virulence gene. YH B. abortus 2308 metH mutant PMID: 14979322 NCBIGene: 3786978 YH UniProtKB accession: Q2YP51 The gene metH from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene metH. B. abortus 2308 pgi mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pgi. Information about the mutated molecule: CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation YH PMID: glycolysis The gene pgi from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YPF3 NCBIGene: 3787092 B. abortus 2308 tig mutant PMID: 14638795 UniProtKB accession: Q2YNL3 The gene tig from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH NCBIGene: 3787589 Information about the mutated molecule: FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene tig. B. abortus 2308 uvrA mutant The gene uvrA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 16816190 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene uvrA. UniProtKB accession: Q2YPX5 Information about the mutated molecule: FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. YH NCBIGene: 3787776 B. abortus 2308 miaA mutant Information about the mutated molecule: FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene miaA. YH NCBIGene: 3787973 UniProtKB accession: Q2YS31 The gene miaA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 12438693 B. abortus 2308 aroC mutant Information about the mutated molecule: CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis The gene aroC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH NCBIGene: 3788622 PMID: chorismate biosynthesis UniProtKB accession: Q2YMF8 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene aroC. B. abortus 2308 aspC mutant Information about the mutated molecule: MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. UniProtKB accession: Q2YRM6 YH NCBIGene: 3788626 The gene aspC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 12761078 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene aspC. B. abortus 2308 bacA mutant The gene bacA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YMA1 Information about the mutated molecule: MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. PMID: 10741969 YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene bacA. NCBIGene: 3788635 B. abortus 2308 cysI mutant UniProtKB accession: Q2YP26 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene cysI. PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. The gene cysI from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH NCBIGene: 3788677 B. abortus 2308 dut mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene dut. UniProtKB accession: Q2YRG4 Information about the mutated molecule: FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). PMID: 12438693 The gene dut from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH NCBIGene: 3788687 B. abortus 2308 glnA mutant PMID: 12438693 Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB accession: Q2YQ67 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene glnA. NCBIGene: 3788725 The gene glnA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH B. abortus 2308 gloA mutant NCBIGene: 3788728 YH PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. UniProtKB accession: Q2YM78 The gene gloA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene gloA. B. abortus 2308 glyA mutant Information about the mutated molecule: FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 3788734 YH The gene glyA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 12438693 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene glyA. UniProtKB accession: Q2YN95 B. abortus 2308 gmd mutant PMID: 15099501 YH The gene gmd from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788735 Information about the mutated molecule: MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene gmd. UniProtKB accession: Q2YMP3 B. abortus 2308 hfq mutant The gene hfq from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YPW9 Information about the mutated molecule: FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. NCBIGene: 3788748 PMID: 14521880, 12730323 YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene hfq. B. abortus 2308 hisC mutant YH PMID: L-histidine biosynthesis The gene hisC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788751 UniProtKB accession: Q2YR81 Information about the mutated molecule: CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene hisC. B. abortus 2308 hisD mutant Information about the mutated molecule: FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene hisD. YH NCBIGene: 3788752 The gene hisD from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: L-histidine biosynthesis UniProtKB accession: Q2YPB8 B. abortus 2308 hisF mutant UniProtKB accession: Q2YQY8 Information about the mutated molecule: FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene hisF. YH PMID: L-histidine biosynthesis NCBIGene: 3788754 The gene hisF from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 hpt mutant UniProtKB accession: Q2YR83 PMID: 14979322 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene hpt. YH The gene hpt from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788755 Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. B. abortus 2308 ilvD mutant The gene ilvD from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: L-isoleucine biosynthesis Information about the mutated molecule: CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis YH NCBIGene: 3788763 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene ilvD. UniProtKB accession: Q2YNW9 B. abortus 2308 leuA mutant NCBIGene: 3788771 The gene leuA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene leuA. UniProtKB accession: Q2YRT1 PMID: L-leucine biosynthesis YH B. abortus 2308 leuC mutant The gene leuC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788772 PMID: L-leucine biosynthesis UniProtKB accession: Q2YLP7 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene leuC. Information about the mutated molecule: FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis YH B. abortus 2308 lysA mutant YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene lysA. NCBIGene: 3788788 UniProtKB accession: Q2YR85 The gene lysA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 12438693 Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. B. abortus 2308 ntrC mutant UniProtKB accession: Q2YPW4 Information about the mutated molecule: MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. NCBIGene: 3788817 YH PMID: 10373105 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene ntrC. The gene ntrC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 ntrY mutant PMID: 10678941 The gene ntrY from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788818 Information about the mutated molecule: MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene ntrY. YH UniProtKB accession: Q2YPW5 B. abortus 2308 omp19 mutant PMID: lipid-anchor(Swiss-Prot: P0A3P2). MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2). SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2). MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. The gene omp19 from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YLR6 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene omp19. YH NCBIGene: 3788831 Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane B. abortus 2308 pepN mutant YH Information about the mutated molecule: MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. PMID: 12933870 UniProtKB accession: Q2YMX0 NCBIGene: 3788843 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pepN. The gene pepN from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 pgm mutant Information about the mutated molecule: MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pgm. YH UniProtKB accession: Q2YPS4 NCBIGene: 3788847 The gene pgm from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 10992476 B. abortus 2308 pheA mutant YH NCBIGene: 3788850 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pheA. UniProtKB accession: Q2YPM5 Information about the mutated molecule: MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. PMID: 15271960 The gene pheA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 pth mutant The gene pth from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 15385478 YH NCBIGene: 3788869 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pth. UniProtKB accession: Q2YLX5 Information about the mutated molecule: FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. B. abortus 2308 purD mutant Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis The gene purD from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene purD. UniProtKB accession: Q2YMD3 YH NCBIGene: 3788874 PMID: IMP biosynthesis B. abortus 2308 purF mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene purF. UniProtKB accession: Q2YMH7 The gene purF from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 12761078 YH NCBIGene: 3788875 Information about the mutated molecule: MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. B. abortus 2308 purH mutant Information about the mutated molecule: CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis NCBIGene: 3788876 PMID: IMP biosynthesis The gene purH from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YLH0 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene purH. YH B. abortus 2308 purM mutant NCBIGene: 3788878 YH The gene purM from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YN59 PMID: IMP biosynthesis A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene purM. Information about the mutated molecule: CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis B. abortus 2308 purN mutant Information about the mutated molecule: MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. NCBIGene: 3788879 YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene purN. UniProtKB accession: Q2YN60 PMID: 12761078 The gene purN from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 pyc mutant UniProtKB accession: Q2YLG1 PMID: 10678941 YH The gene pyc from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pyc. Information about the mutated molecule: MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. NCBIGene: 3788880 B. abortus 2308 pyrD mutant UniProtKB accession: Q2YPG3 Information about the mutated molecule: MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. The gene pyrD from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pyrD. NCBIGene: 3788883 PMID: 12761078 YH B. abortus 2308 recA mutant Information about the mutated molecule: FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993]. NCBIGene: 3788897 YH The gene recA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene recA. PMID: 8321120 UniProtKB accession: Q2YRU7 B. abortus 2308 rfbD mutant Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. The gene rfbD from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 14979322 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene rfbD. YH UniProtKB accession: Q2YMP5 NCBIGene: 3788901 B. abortus 2308 rplS mutant NCBIGene: 3788922 UniProtKB accession: Q2YLP6 The gene rplS from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. PMID: 15271960 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene rplS. YH B. abortus 2308 rpoA mutant The gene rpoA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788935 UniProtKB accession: Q2YRU0 YH PMID: 14638795 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene rpoA. Information about the mutated molecule: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. B. abortus 2308 rpsA mutant The gene rpsA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YPN4 PMID: 10678941 NCBIGene: 3788939 YH Information about the mutated molecule: MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene rpsA. B. abortus 2308 flgE mutant The gene flgE from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene flgE. UniProtKB accession: Q2YJF9 YH Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIGene: 3827409 B. abortus 2308 motB mutant NCBIGene: 3827414 Information about the mutated molecule: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 The gene motB from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene motB. UniProtKB accession: Q2YJF4 B. abortus 2308 ugpA mutant YH UniProtKB accession: Q2YKR6 PMID: 14638795 NCBIGene: 3827693 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene ugpA. Information about the mutated molecule: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. The gene ugpA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 ugpB mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene ugpB. UniProtKB accession: Q2YKR5 YH PMID: 16817909 The gene ugpB from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. NCBIGene: 3827694 B. abortus 2308 znuA mutant The gene znuA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YJH5 Information about the mutated molecule: MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. YH NCBIGene: 3827700 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene znuA. PMID: 12761078 B. abortus 2308 znuC mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene znuC. The gene znuC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 14979322 YH Information about the mutated molecule: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 3827702 UniProtKB accession: Q2YJH4 B. abortus 2308 nrdH mutant The gene nrdH from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 14979322 UniProtKB accession: Q2YJZ1 YH Information about the mutated molecule: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene nrdH. NCBIGene: 3827703 B. abortus 2308 pyrB mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pyrB. NCBIGene: 3827823 Information about the mutated molecule: CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis YH UniProtKB accession: Q2YKL8 PMID: UMP biosynthesis The gene pyrB from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 sodC mutant PMID: 10816475 Information about the mutated molecule: FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. The gene sodC from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. UniProtKB accession: Q2YKV9 NCBIGene: 3827840 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene sodC. YH B. abortus 2308 virB8 mutant UniProtKB accession: Q2YJ78 YH NCBIGene: 3827898 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene virB8. Information about the mutated molecule: MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. PMID: 10678941, 12414149 The gene virB8 from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. B. abortus 2308 xseA mutant UniProtKB accession: Q2YL15 PMID: 14638795 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene xseA. YH The gene xseA from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. NCBIGene: 3827916 B. abortus 2308 narG mutant PMID: 12438693 UniProtKB accession: Q2YJY4 The gene narG from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene narG. NCBIGene: 3827924 Information about the mutated molecule: MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. B. abortus 2308 virB5 mutant NCBIGene: 3827978 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene virB5. The gene virB5 from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: 12595417, 12595466, 16113325, 10510235 UniProtKB accession: Q2YJ75 YH Information about the mutated molecule: MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. B. abortus 2308 virB3 mutant The gene virB3 from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. YH PMID: 12761078 UniProtKB accession: Q2YIT7 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene virB3. NCBIGene: 3827980 B. abortus 2308 virB2 mutant UniProtKB accession: Q2YIT6 The gene virB2 from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH Information about the mutated molecule: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. PMID: 15322008, 16113325 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene virB2. NCBIGene: 3827981 B. abortus 2308 omp10 mutant UniProtKB accession: Q2YIP8 Information about the mutated molecule: SUBCELLULAR LOCATION: Outer membrane PMID: lipid-anchor(Swiss-Prot: P0A3N9). MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9). SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9). MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. The gene omp10 from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene omp10. NCBIGene: 3828036 B. abortus 2308 cydB mutant PMID: 11274104 YH Information about the mutated molecule: MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene cydB. UniProtKB accession: Q2YKD5 The gene cydB from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3828142 B. abortus 2308 divK mutant PMID: 14979322 Information about the mutated molecule: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. YH NCBIGene: 3828149 The gene divK from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene divK. UniProtKB accession: Q2YKN1 B. abortus 2308 fliF mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene fliF. PMID: multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3). SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3). MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. NCBIGene: 3828220 The gene fliF from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane YH UniProtKB accession: Q2YJF2 B. abortus 2308 gcvP mutant The gene gcvP from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3828233 UniProtKB accession: Q2YKX9 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene gcvP. Information about the mutated molecule: FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor PMID: CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-Prot: Q8FVU9). CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-Prot: Q8FVU9). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FVU9). SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-Prot: Q8FVU9). SIMILARITY: Belongs to the gcvP family(Swiss-Prot: Q8FVU9). MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ref6482:Ficht, 2003]. YH B. abortus 2308 gcvT mutant YH The gene gcvT from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 3828234 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene gcvT. PMID: 12438693 UniProtKB accession: Q2YKY1 B. abortus 2308 gltD mutant The gene gltD from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3828240 YH Information about the mutated molecule: MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. PMID: 10858227 A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene gltD. UniProtKB accession: Q2YJ86 B. abortus 2308 gnd mutant NCBIGene: 3828241 The gene gnd from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. Information about the mutated molecule: MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. UniProtKB accession: Q2YJ89 PMID: 12761078 YH A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene gnd. B. abortus 2308 hemH mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene hemH. The gene hemH from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. PMID: last step(Swiss-Prot: P0A3D7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7). SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7). MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. NCBIGene: 3828247 UniProtKB accession: Q2YIS9 Information about the mutated molecule: FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis YH B. melitensis 16M BMEI0066 mutant YH A mutant of strain Brucella melitensis 16M that lacks an intact gene BMEI0066. The gene BMEI0066 from the strain Brucella melitensis 16M is a virulence gene. NCBIGene: 1195778 UniProtKB accession: Q8YJL6 PMID: 19742243 Information about the mutated molecule: MUTATION: BMEI0066 deletion mutant fails to replicated in murine macrophages and is rapidly cleared from the spleens of experimentally infected BALB/c mice [Ref7314:Zhang et al., 2009]. B. abortus 2308 asp24 mutant A mutant of strain Brucella abortus S2308 that lacks an intact gene asp24. NCBIGene: 3787926 YH PMID: 17664263 Information about the mutated molecule: MUTATION: A asp24 mutation in Brucella abortus is attenuated in mice [Ref7373:Kahl-McDonagh et al., 2007]. UniProtKB accession: Q2YQE8 The gene asp24 from the strain Brucella abortus S2308 is a virulence gene. B. melitensis 16M bp26 mutant Information about the mutated molecule: MUTATION: A bp26 mutant in Brucella melitensis was attenuated in mice [Ref7374:Cloeckaert et al., 2004]. YH NCBIGene: 1196247 A mutant of strain Brucella melitensis 16M that lacks an intact gene bp26. UniProtKB accession: P0A3U8 PMID: 15246618 The gene bp26 from the strain Brucella melitensis 16M is a virulence gene. B. abortus 2308 pgk mutant A mutant of strain Brucella melitensis biovar Abortus 2308 that lacks an intact gene pgk. PMID: 20194591 Information about the mutated molecule: MUTATION: A pgk mutant is attenuated in mice [Ref7376:Trant et al., 2010]. YH The gene pgk from the strain Brucella melitensis biovar Abortus 2308 is a virulence gene. NCBIGene: 3788256 UniProtKB accession: Q2YRD9 Brucella suis bv. 1 str. S2 Brucella suis bv. 1 str. S2 Brucella suis bv. 1 strain S2 Brucella melitensis bv. 1 str. M111 Brucella melitensis bv. 1 str. M111 Brucella melitensis bv. 1 strain M111 Brucella melitensis bv. 1 str. M28-12 Brucella melitensis bv. 1 str. M28-12 Brucella melitensis bv. 1 strain M28-12 Brucella melitensis bv. 1 str. M5 Brucella melitensis bv. 1 str. M5 Brucella melitensis bv. 1 strain M5 Muridae Muridae Mus <mouse, genus> Mus Mus <mouse, genus> mice Mus musculus Mus musculus house mouse mouse Viruses Viruses Viruses Viruses Brucella melitensis NI Brucella melitensis NI Brucella melitensis str. NI Brucella melitensis strain NI Brucella sp. CMC Brucella sp. CMC Brucella abortus bv. 1 str. NI435a Brucella abortus bv. 1 str. NI435a Brucella abortus bv. 1 strain NI435a Brucella abortus bv. 1 str. NI474 Brucella abortus bv. 1 str. NI474 Brucella abortus bv. 1 strain NI474 Brucella abortus bv. 1 str. NI486 Brucella abortus bv. 1 str. NI486 Brucella abortus bv. 1 strain NI486 Brucella abortus bv. 1 str. NI488 Brucella abortus bv. 1 str. NI488 Brucella abortus bv. 1 strain NI488 Brucella abortus bv. 1 str. NI010 Brucella abortus bv. 1 str. NI010 Brucella abortus bv. 1 strain NI010 Brucella abortus bv. 1 str. NI016 Brucella abortus bv. 1 str. NI016 Brucella abortus bv. 1 strain NI016 Brucella abortus bv. 1 str. NI021 Brucella abortus bv. 1 str. NI021 Brucella abortus bv. 1 strain NI021 Brucella abortus bv. 1 str. NI259 Brucella abortus bv. 1 str. NI259 Brucella abortus bv. 1 strain NI259 Brucella sp. 02/611 Brucella sp. 02/611 Brucella sp. 4986/3 Brucella sp. 4986/3 Brucella sp. 5541/1 Brucella sp. 5541/1 Brucella abortus A13334 Brucella abortus A13334 Brucella canis HSK A52141 Brucella canis HSK A52141 Brucella canis str. HSK A52141 Brucella canis strain HSK A52141 Brucella sp. 152 Brucella sp. 152 Brucella suis VBI22 Brucella suis VBI22 Brucella suis str. VBI22 Brucella suis strain VBI22 Brucella sp. N37 Brucella sp. N37 Brucella sp. LK4-1 Brucella sp. LK4-1 Brucella melitensis 16M1W Brucella melitensis 16M1W Brucella melitensis 16M13W Brucella melitensis 16M13W Brucella sp. 1312 Brucella sp. 1312 Brucella sp. 96-408 Brucella sp. 96-408 Brucella melitensis S66 Brucella melitensis S66 Brucella melitensis str. S66 Brucella melitensis strain S66 Brucella sp. 09RB8471 Brucella sp. 09RB8471 Brucella sp. 10RB9215 Brucella sp. 10RB9215 Brucella abortus NI628 Brucella abortus NI628 Brucella abortus NI518 Brucella abortus NI518 Brucella abortus NI649 Brucella abortus NI649 Brucella abortus NI240 Brucella abortus NI240 Brucella abortus NI274 Brucella abortus NI274 Brucella abortus NI352 Brucella abortus NI352 Brucella abortus NI380 Brucella abortus NI380 Brucella abortus NI388 Brucella abortus NI388 Brucella abortus NI422 Brucella abortus NI422 Brucella abortus NI492 Brucella abortus NI492 Brucella abortus NI495a Brucella abortus NI495a Brucella abortus NI593 Brucella abortus NI593 Brucella abortus NI613 Brucella abortus NI613 Brucella abortus NI622 Brucella abortus NI622 Brucella abortus NI633 Brucella abortus NI633 Brucella abortus NI639 Brucella abortus NI639 Brucella abortus NI645 Brucella abortus NI645 Brucella abortus 63/168 Brucella abortus 63/168 Brucella abortus 88/19 Brucella abortus 88/19 Brucella abortus 85/69 Brucella abortus 85/69 Brucella abortus F6/05-2 Brucella abortus F6/05-2 Brucella abortus 63/294 Brucella abortus 63/294 Brucella abortus 67/781 Brucella abortus 67/781 Brucella abortus 63/59 Brucella abortus 63/59 Brucella abortus F3/07-1 Brucella abortus F3/07-1 Brucella abortus 80/101 Brucella abortus 80/101 Brucella abortus 63/183 Brucella abortus 63/183 Brucella abortus 85/140 Brucella abortus 85/140 Brucella abortus F6/05-4 Brucella abortus F6/05-4 Brucella abortus 78/36 Brucella abortus 78/36 Brucella abortus I103 Brucella abortus I103 Brucella abortus F1/06 B1 Brucella abortus F1/06 B1 Brucella abortus F2/06-8 Brucella abortus F2/06-8 Brucella abortus 863/67 Brucella abortus 863/67 Brucella abortus 88/226 Brucella abortus 88/226 Brucella abortus F3/01 Brucella abortus F3/01 Brucella abortus 90/50 Brucella abortus 90/50 Brucella abortus 93/1 Brucella abortus 93/1 Brucella abortus 80/108 Brucella abortus 80/108 Brucella abortus 64/108 Brucella abortus 64/108 Brucella abortus 65/157 Brucella abortus 65/157 Brucella abortus levi gila Brucella abortus levi gila Brucella abortus F5/04-7 Brucella abortus F5/04-7 Brucella abortus 80/102 Brucella abortus 80/102 Brucella abortus LEVI237 Brucella abortus LEVI237 Brucella abortus 64/122 Brucella abortus 64/122 Brucella abortus 877/67 Brucella abortus 877/67 Brucella abortus F6/05-3 Brucella abortus F6/05-3 Brucella abortus F6/05-9 Brucella abortus F6/05-9 Brucella abortus 65/110 Brucella abortus 65/110 Brucella melitensis F3/02 Brucella melitensis F3/02 Brucella melitensis F10/05-2 Brucella melitensis F10/05-2 Brucella melitensis 63/227 Brucella melitensis 63/227 Brucella melitensis UK23/06 Brucella melitensis UK23/06 Brucella melitensis UK22/04 Brucella melitensis UK22/04 Brucella melitensis F5/07-239A Brucella melitensis F5/07-239A Brucella melitensis UK37/05 Brucella melitensis UK37/05 Brucella melitensis UK14/06 Brucella melitensis UK14/06 Brucella melitensis R3/07-2 Brucella melitensis R3/07-2 Brucella melitensis F1/06 B10 Brucella melitensis F1/06 B10 Brucella melitensis 64/150 Brucella melitensis 64/150 Brucella melitensis UK22/06 Brucella melitensis UK22/06 Brucella melitensis Uk24/06 Brucella melitensis Uk24/06 Brucella melitensis UK19/04 Brucella melitensis UK19/04 Brucella melitensis 66/59 Brucella melitensis 66/59 Brucella melitensis F8/01-155 Brucella melitensis F8/01-155 Brucella melitensis F2/06-6 Brucella melitensis F2/06-6 Brucella suis 63/198 Brucella suis 63/198 Brucella suis 63/261 Brucella suis 63/261 Brucella suis F12/02 Brucella suis F12/02 Brucella suis 92/63 Brucella suis 92/63 Brucella suis F8/06-2 Brucella suis F8/06-2 Brucella suis 63/252 Brucella suis 63/252 Brucella suis 92/29 Brucella suis 92/29 Brucella sp. UK38/05 Brucella sp. UK38/05 Brucella sp. 63/311 Brucella sp. 63/311 Brucella abortus 225/65 Brucella abortus 225/65 Brucella abortus 355/78 Brucella abortus 355/78 Brucella abortus 544 Brucella abortus 544 Brucella abortus 600/64 Brucella abortus 600/64 Brucella abortus 63/130 Brucella abortus 63/130 Brucella abortus 63/138 Brucella abortus 63/138 Brucella abortus 63/144 Brucella abortus 63/144 Brucella abortus 64/81 Brucella abortus 64/81 Brucella abortus 65/63 Brucella abortus 65/63 Brucella abortus 67/93 Brucella abortus 67/93 Brucella abortus 78/14 Brucella abortus 78/14 Brucella abortus 80/28 Brucella abortus 80/28 Brucella abortus 84/26 Brucella abortus 84/26 Brucella abortus 87/28 Brucella abortus 87/28 Brucella abortus 93/2 Brucella abortus 93/2 Brucella abortus F1/06-B21 Brucella abortus F1/06-B21 Brucella abortus F10/05-11 Brucella abortus F10/05-11 Brucella abortus F10/06-3 Brucella abortus F10/06-3 Brucella abortus R42-08 Brucella abortus R42-08 Brucella canis 79/122 Brucella canis 79/122 Brucella canis str. 79/122 Brucella canis strain 79/122 Brucella melitensis BG2 (S27) Brucella melitensis BG2 (S27) Brucella melitensis F10/06-16 Brucella melitensis F10/06-16 Brucella melitensis F6/05-6 Brucella melitensis F6/05-6 Brucella melitensis F9/05 Brucella melitensis F9/05 Brucella melitensis UK29/05 Brucella melitensis UK29/05 Brucella melitensis UK3/06 Brucella melitensis UK3/06 Brucella melitensis UK31/99 Brucella melitensis UK31/99 Brucella ovis 63/96 Brucella ovis 63/96 Brucella ovis 80/125 Brucella ovis 80/125 Brucella ovis 81/8 Brucella ovis 81/8 Brucella sp. F5/06 Brucella sp. F5/06 Brucella sp. 56/94 Brucella sp. 56/94 Brucella suis F5/05-10 Brucella suis F5/05-10 Brucella suis str. F5/05-10 Brucella suis strain F5/05-10 Brucella suis F5/03-2 Brucella suis F5/03-2 Brucella suis F5/05-4 Brucella suis F5/05-4 Brucella suis F7/06-1 Brucella suis F7/06-1 Brucella suis F7/06-2 Brucella suis F7/06-2 Brucella suis F7/06-5 Brucella suis F7/06-5 Brucella suis F8/06-1 Brucella suis F8/06-1 Brucella suis F8/06-3 Brucella suis F8/06-3 Brucella suis F9/06-1 Brucella suis F9/06-1 Brucella suis 01-5744 Brucella suis 01-5744 Brucella suis str. 01-5744 Brucella suis strain 01-5744 Brucella suis 019 Brucella suis 019 Brucella suis str. 019 Brucella suis strain 019 Teleostomi Teleostomi Euteleostomi Euteleostomi bony vertebrates Brucella sp. CMC-2 Brucella sp. CMC-2 Brucellaceae Brucellaceae Brucella ovis F8/05B Brucella ovis F8/05B Brucella melitensis CNGB 1076 Brucella melitensis CNGB 1076 Brucella melitensis CNGB 1120 Brucella melitensis CNGB 1120 Brucella melitensis CNGB 290 Brucella melitensis CNGB 290 Brucella suis CNGB 786 Brucella suis CNGB 786 Brucella suis CNGB 247 Brucella suis CNGB 247 Brucella canis CNGB 1324 Brucella canis CNGB 1324 Brucella canis CNGB 513 Brucella canis CNGB 513 Brucella canis CNGB 1172 Brucella canis CNGB 1172 Brucella abortus CNGB 436 Brucella abortus CNGB 436 Brucella abortus CNGB 308 Brucella abortus CNGB 308 Brucella abortus CNGB 752 Brucella abortus CNGB 752 Brucella abortus CNGB 759 Brucella abortus CNGB 759 Brucella abortus CNGB 966 Brucella abortus CNGB 966 Brucella abortus CNGB 1011 Brucella abortus CNGB 1011 Brucella abortus CNGB 1432 Brucella abortus CNGB 1432 Brucella suis F4/06-146 Brucella suis F4/06-146 Brucella suis 94/11 Brucella suis 94/11 Brucella canis UK10/02 Brucella canis UK10/02 Brucella abortus 88/217 Brucella abortus 88/217 Brucella abortus 78/32 Brucella abortus 78/32 Brucella canis F7/05A Brucella canis F7/05A Brucella abortus RB51-AHVLA Brucella abortus RB51-AHVLA Brucella abortus str. RB51-AHVLA Brucella abortus strain RB51-AHVLA Brucella pinnipedialis Brucella pinnipedialis Brucella ceti Brucella ceti Brucella suis bv. 1 str. BCB025 Brucella suis bv. 1 str. BCB025 Brucella canis BCB018 Brucella canis BCB018 Brucella abortus bv. 1 str. BCB027 Brucella abortus bv. 1 str. BCB027 Brucella melitensis bv. 1 str. BCB028 Brucella melitensis bv. 1 str. BCB028 Brucella suis bv. 2 str. BCB032 Brucella suis bv. 2 str. BCB032 Brucella melitensis bv. 1 str. BCB033 Brucella melitensis bv. 1 str. BCB033 Brucella abortus bv. 2 str. BCB034 Brucella abortus bv. 2 str. BCB034 Brucella abortus bv. 1 str. BCB013 Brucella abortus bv. 1 str. BCB013 Brucella melitensis M5-10 Brucella melitensis M5-10 Brucella suis S2-30 Brucella suis S2-30 Brucella abortus 104M Brucella abortus 104M Brucella inopinata Brucella inopinata Proteobacteria Proteobacteria purple bacteria purple bacteria and relatives purple non-sulfur bacteria purple photosynthetic bacteria purple photosynthetic bacteria and relatives Brucella canis 118 Brucella canis 118 Brucella melitensis bv. 3 str. 128 Brucella melitensis bv. 3 str. 128 Brucella melitensis bv. 1 str. 133 Brucella melitensis bv. 1 str. 133 Brucella abortus bv. 1 str. 134 Brucella abortus bv. 1 str. 134 Brucella abortus F3/01-300 Brucella abortus F3/01-300 Brucella sp. AO-1 Brucella sp. AO-1 Brucella melitensis F15/06-7 Brucella melitensis F15/06-7 Brucella melitensis B115 Brucella melitensis B115 Brucella melitensis str. B115 Brucella melitensis strain B115 Brucella sp. 88S Brucella sp. 88S Brucella melitensis 043 Brucella melitensis 043 Brucella sp. 7763/2 Brucella sp. 7763/2 Bacteria Bacteria Bacteria GC_ID:11 Monera PMID:10425795 PMID:10425796 PMID:10425797 PMID:10490293 PMID:10843050 PMID:10939651 PMID:10939673 PMID:10939677 PMID:11211268 PMID:11321083 PMID:11321113 PMID:11411719 PMID:11540071 PMID:11542017 PMID:11542087 PMID:11760965 PMID:12054223 PMID:2112744 PMID:270744 PMID:8123559 PMID:8590690 PMID:9103655 PMID:9336922 Procaryotae Prokaryota Prokaryotae bacteria eubacteria eubacteria ncbi_taxonomy not Bacteria Haeckel 1894 prokaryote prokaryotes Brucella suis 1330 Brucella melitensis biovar Suis str. 1330 Brucella suis 1330 Brucella suis ATCC 23444 Brucella suis NCTC 10316 Brucella suis str. 1330 Brucella suis str. 1330 GC_ID:11 PMID:12271122 ncbi_taxonomy Homininae Homininae Archaea Archaea Archaea Brucella melitensis bv. 1 str. 16M Brucella melitensis 16M Brucella melitensis ATCC 23456 Brucella melitensis bv. 1 str. 16M Brucella melitensis str. 16M Brucella melitensis str. ATCC 23456 GC_ID:11 PMID:11756688 ncbi_taxonomy Brucella melitensis bv. 1 str. 16M Brucella Brucella Brucella Meyer and Shaw 1920 GC_ID:11 PMID:8573514 ncbi_taxonomy Brucella is a genus of Gram-negative bacteria.[1] They are small (0.5 to 0.7 by 0.6 to 1.5), non-motile, non-encapsulated coccobacilli, which function as facultative intracellular parasites. Brucella is the cause of brucellosis, which is a zoonosis. It is transmitted by ingesting infected food, direct contact with an infected animal, or inhalation of aerosols. Transmission from human to human, for example through sexual intercourse or from mother to child, is exceedingly rare, but possible.[2] Minimum infectious exposure is between 10 - 100 organisms. Brucellosis primarily occurs through occupational exposure (e.g. exposure to cattle, sheep, pigs), but also by consumption of unpasteurized milk products. There are a few different species of Brucella, each with slightly different host specificity. B.melitensis which infects goats and sheep, B. abortus which infects cattle, B. suis infects pigs, B.ovis infects sheep and B.neotomae. Recently new species were discovered, in marine mammals (B.pinnipedialis and B.ceti ), in the common vole Microtus arvalis (B.microti ), and even in a breast implant (B.inopinata ). However, the new NCBI taxonomy has named all Brucella species Brucella melitensis. They include Brucella melitensis 16M and 5 other biovars: abortus, canis, neotomae, ovis, and suis. http://en.wikipedia.org/wiki/Brucella Brucella abortus Brucella abortus Brucella melitensis bv. Abortus Brucella ovis Brucella melitensis bv. Ovis Brucella ovis Brucella sp. mp-7 Brucella sp. mp-7 Brucella sp. JM13/00 Brucella sp. JM13/00 Brucella abortus bv. 1 str. 9-941 Brucella abortus biovar 1 str. 9-941 Brucella abortus bv. 1 str. 9-941 Brucella abortus bv. 1 strain 9-941 Brucella melitensis biovar Melitensis Brucella melitensis biovar Melitensis Brucella melitensis bv. Melitensis Eukaryota Eukaryota Eukaryota eucaryotes eukaryotes Bovinae Bovinae Alphaproteobacteria Alphaproteobacteria Brucella melitensis Brucella melitensis most common cause of human brucellosis Brucella neotomae Brucella melitensis bv. Neotomae Brucella neotomae Brucella suis Brucella melitensis bv. Suis Brucella suis Laurasiatheria Laurasiatheria Euarchontoglires Euarchontoglires Glires Glires Rodents and rabbits Simiiformes Simiiformes Cercopithecoidea Cercopithecoidea Hominoidea Hominoidea ape apes Tetrapoda Tetrapoda tetrapods Amniota Amniota amniotes Theria <Mammalia> Theria Theria <Mammalia> Opisthokonta Fungi/Metazoa group Opisthokonta Fungi/Metazoa group Metazoa Metazoa metazoans multicellular animals Bilateria Bilateria Deuterostomia Deuterostomia Sciurognathi Sciurognathi Carnivora Carnivora carnivores Muroidea Muroidea Brucella sp. HJ114 Brucella sp. HJ114 Brucella sp. R-26895 Brucella sp. R-26895 Suina Suina Pecora Pecora Equus <subgenus> Equus Equus <subgenus> Rhizobiales Rhizobiales rhizobacteria Brucella abortus bv. 1 Brucella abortus 1 Brucella abortus biovar 1 Brucella abortus bv. 1 Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus 2308 Brucella melitensis biovar Abortus str. 2308 Brucella melitensis biovar Abortus str. 2308 Brucella melitensis biovar Abortus strain 2308 Brucella melitensis biovar Abortus strain 2308 GC_ID:11 PMID:16299333 PMID:20462421 ncbi_taxonomy Brucella sp. YBJCA-1 Brucella sp. YBJCA-1 Brucella sp. CGL-1 Brucella sp. CGL-1 Brucella sp. SSO-1 Brucella sp. SSO-1 Brucella canis Brucella canis Brucella melitensis bv. Canis it is very rare cause of human brucellosis Brucella sp. HPC1135 Brucella sp. HPC1135 Haplorrhini Haplorrhini Caniformia Caniformia Brucella sp. DMA Brucella sp. DMA Murinae Murinae Chlorocebus Chlorocebus Brucella sp. 02611 Brucella sp. 02611 Brucella sp. F599 Brucella sp. F599 Mammalia Mammalia mammals Brucella abortus S19 Brucella abortus S19 Brucella abortus str. S19 Brucella abortus strain S19 Brucella sp. GXY-1 Brucella sp. GXY-1 Brucella sp. AUBY47 Brucella sp. AUBY47 Brucella sp. 36/94 Brucella sp. 36/94 Brucella sp. 52/94 Brucella sp. 52/94 Brucella sp. UK15/98 Brucella sp. UK15/98 Brucella sp. UK35/99 Brucella sp. UK35/99 Brucella sp. 14/95 Brucella sp. 14/95 Brucella sp. 2/96 Brucella sp. 2/96 Brucella sp. UK1/97 Brucella sp. UK1/97 Brucella sp. UK3/97 Brucella sp. UK3/97 Brucella sp. UK5/97 Brucella sp. UK5/97 Brucella sp. UK10/00 Brucella sp. UK10/00 Brucella sp. UK4/01 Brucella sp. UK4/01 Brucella sp. UK10/01 Brucella sp. UK10/01 Brucella sp. UK15/02 Brucella sp. UK15/02 Brucella sp. F23/97 Brucella sp. F23/97 Brucella sp. F96/2 Brucella sp. F96/2 Brucella sp. VLA04.67 Brucella sp. VLA04.67 Brucella sp. VLA04.72 Brucella sp. VLA04.72 Brucella sp. VLA04/105 Brucella sp. VLA04/105 Brucella sp. VLA04/06 Brucella sp. VLA04/06 Brucella sp. UK31/04 Brucella sp. UK31/04 Brucella sp. 39/94 Brucella sp. 39/94 Brucella sp. 44/94 Brucella sp. 44/94 Brucella sp. UK24/00 (M192) Brucella sp. UK24/00 (M192) Brucella sp. 55/94 Brucella sp. 55/94 Brucella sp. 4/96 Brucella sp. 4/96 Brucella sp. 61/94 Brucella sp. 61/94 Brucella sp. UK13/99 Brucella sp. UK13/99 Brucella sp. UK40/99 Brucella sp. UK40/99 Brucella sp. UK5/01 Brucella sp. UK5/01 Brucella sp. F6/99 Brucella sp. F6/99 Brucella sp. F8/99 Brucella sp. F8/99 Brucella sp. F9/99 Brucella sp. F9/99 Brucella sp. F10/99 Brucella sp. F10/99 Brucella sp. F7/99 Brucella sp. F7/99 Brucella sp. UK28/03-13840 Brucella sp. UK28/03-13840 Brucella sp. 59/94 Brucella sp. 59/94 Brucella sp. 5/95 Brucella sp. 5/95 Brucella sp. UK43/99 Brucella sp. UK43/99 Brucella sp. UK1/2000 Brucella sp. UK1/2000 Brucella sp. UK2/2000 Brucella sp. UK2/2000 Brucella sp. 14/94 Brucella sp. 14/94 Brucella sp. UK3/05 Brucella sp. UK3/05 Brucella sp. VLA05/4 Brucella sp. VLA05/4 Brucella sp. VLA05/8 Brucella sp. VLA05/8 Brucella sp. F5/99 Brucella sp. F5/99 Brucella sp. F5/02 Brucella sp. F5/02 Brucella microti Brucella microti Brucella ovis ATCC 25840 Brucella ovis ATCC 25840 Brucella ovis str. ATCC 25840 Brucella ovis strain ATCC 25840 Brucella suis ATCC 23445 Brucella suis ATCC 23445 Brucella suis str. ATCC 23445 Brucella suis strain ATCC 23445 Brucella inopinata BO1 Brucella inopinata BO1 Brucella canis ATCC 23365 Brucella canis ATCC 23365 Brucella canis str. ATCC 23365 Brucella canis strain ATCC 23365 Brucella sp. DB-6 Brucella sp. DB-6 Brucella sp. NVSL 07-0026 Brucella sp. NVSL 07-0026 Brucella sp. 83/13 Brucella sp. 83/13 Brucella abortus bv. 2 str. 86/8/59 Brucella abortus bv. 2 str. 86/8/59 Brucella abortus bv. 3 str. Tulya Brucella abortus bv. 3 str. Tulya Brucella abortus bv. 4 str. 292 Brucella abortus bv. 4 str. 292 Brucella abortus bv. 5 str. B3196 Brucella abortus bv. 5 str. B3196 Brucella abortus bv. 6 str. 870 Brucella abortus bv. 6 str. 870 Brucella abortus bv. 9 str. C68 Brucella abortus bv. 9 str. C68 Brucella neotomae 5K33 Brucella neotomae 5K33 Brucella ceti B1/94 Brucella ceti B1/94 Brucella ceti M490/95/1 Brucella ceti M490/95/1 Brucella ceti M644/93/1 Brucella ceti M644/93/1 Brucella ceti M13/05/1 Brucella ceti M13/05/1 Brucella pinnipedialis B2/94 Brucella pinnipedialis B2/94 Brucella pinnipedialis M292/94/1 Brucella pinnipedialis M292/94/1 Brucella pinnipedialis M163/99/10 Brucella pinnipedialis M163/99/10 Brucella melitensis bv. 1 str. Rev.1 Brucella melitensis bv. 1 str. Rev.1 Brucella melitensis bv. 2 str. 63/9 Brucella melitensis bv. 2 str. 63/9 Brucella melitensis bv. 3 str. Ether Brucella melitensis bv. 3 str. Ether Brucella melitensis bv. 1 str. 63/149 Brucella melitensis bv. 1 str. 63/149 Brucella melitensis bv. 1 str. 63/33 Brucella melitensis bv. 1 str. 63/33 Brucella melitensis bv. 1 str. 63/143 Brucella melitensis bv. 1 str. 63/143 Brucella melitensis bv. 1 str. 63/43 Brucella melitensis bv. 1 str. 63/43 Brucella melitensis bv. 1 str. 63/61 Brucella melitensis bv. 1 str. 63/61 Brucella melitensis bv. 1 str. 65/16 Brucella melitensis bv. 1 str. 65/16 Brucella melitensis bv. 1 str. 65/57 Brucella melitensis bv. 1 str. 65/57 Brucella melitensis bv. 1 str. 65/56 Brucella melitensis bv. 1 str. 65/56 Brucella melitensis bv. 1 str. 65/32 Brucella melitensis bv. 1 str. 65/32 Brucella melitensis bv. 1 str. 65/112 Brucella melitensis bv. 1 str. 65/112 Brucella melitensis bv. 1 str. 65/61 Brucella melitensis bv. 1 str. 65/61 Brucella melitensis bv. 1 str. 80/1 Brucella melitensis bv. 1 str. 80/1 Brucella melitensis bv. 1 str. 80/4 Brucella melitensis bv. 1 str. 80/4 Brucella melitensis bv. 1 str. 85/20 Brucella melitensis bv. 1 str. 85/20 Brucella melitensis bv. 1 str. 90/1 Brucella melitensis bv. 1 str. 90/1 Brucella melitensis bv. 1 str. F3/99-548 Brucella melitensis bv. 1 str. F3/99-548 Brucella melitensis bv. 1 str. F1/01 Brucella melitensis bv. 1 str. F1/01 Brucella melitensis bv. 1 str. R36/03-60 Brucella melitensis bv. 1 str. R36/03-60 Brucella melitensis bv. 1 str. F3/05-371 Brucella melitensis bv. 1 str. F3/05-371 Brucella melitensis bv. 1 str. F3/05-372 Brucella melitensis bv. 1 str. F3/05-372 Brucella suis bv. 3 str. 686 Brucella suis bv. 3 str. 686 Brucella suis bv. 4 str. 40 Brucella suis bv. 4 str. 40 Brucella suis bv. 5 str. 513 Brucella suis bv. 5 str. 513 Brucella suis bv. 1 str. 63/177 Brucella suis bv. 1 str. 63/177 Brucella suis bv. 1 str. 63/142 Brucella suis bv. 1 str. 63/142 Brucella suis bv. 1 str. 63/178 Brucella suis bv. 1 str. 63/178 Brucella suis bv. 1 str. 63/32 Brucella suis bv. 1 str. 63/32 Brucella suis bv. 1 str. 63/24 Brucella suis bv. 1 str. 63/24 Brucella suis bv. 1 str. 63/169 Brucella suis bv. 1 str. 63/169 Brucella suis bv. 1 str. 63/166 Brucella suis bv. 1 str. 63/166 Brucella suis bv. 1 str. 63/171 Brucella suis bv. 1 str. 63/171 Brucella suis bv. 1 str. 63/238 Brucella suis bv. 1 str. 63/238 Brucella suis bv. 1 str. 64/24 Brucella suis bv. 1 str. 64/24 Brucella suis bv. 1 str. 74/10 Brucella suis bv. 1 str. 74/10 Brucella suis bv. 1 str. 76/4 Brucella suis bv. 1 str. 76/4 Brucella suis bv. 1 str. 79/224 Brucella suis bv. 1 str. 79/224 Brucella suis bv. 1 str. 80/146 Brucella suis bv. 1 str. 80/146 Brucella suis bv. 1 str. 81/27 Brucella suis bv. 1 str. 81/27 Brucella suis bv. 1 str. 88/114 Brucella suis bv. 1 str. 88/114 Brucella suis bv. 1 str. 88/45 Brucella suis bv. 1 str. 88/45 Brucella suis bv. 1 str. 92/29 Brucella suis bv. 1 str. 92/29 Brucella suis bv. 1 str. F7/03-BSI Brucella suis bv. 1 str. F7/03-BSI Brucella suis bv. 1 str. F6/04 Brucella suis bv. 1 str. F6/04 Brucella sp. Brucella sp. Brucella abortus bv. 3 Brucella abortus biovar 3 Brucella abortus bv. 3 Brucella abortus F4902 Brucella abortus F4902 Brucella abortus bv. 1 str. 2256#1042 Brucella abortus bv. 1 str. 2256#1042 Brucella abortus bv. 1 str. 2042#1006 Brucella abortus bv. 1 str. 2042#1006 Brucella abortus bv. 1 str. 3#1332 Brucella abortus bv. 1 str. 3#1332 Brucella abortus bv. 1 str. 2032#1004 Brucella abortus bv. 1 str. 2032#1004 Brucella abortus bv. 1 str. 8-953#1146 Brucella abortus bv. 1 str. 8-953#1146 Brucella abortus bv. 1 str. 2054#1021 Brucella abortus bv. 1 str. 2054#1021 Brucella abortus bv. 1 str. 2051#1011 Brucella abortus bv. 1 str. 2051#1011 Brucella abortus bv. 1 str. 2038#1019 Brucella abortus bv. 1 str. 2038#1019 Brucella melitensis bv. 3 str. G9481 Brucella melitensis bv. 3 str. G9481 Brucella melitensis bv. 1 str. G5013 Brucella melitensis bv. 1 str. G5013 Brucella melitensis bv. 1 str. H0866 Brucella melitensis bv. 1 str. H0866 Brucella melitensis bv. 1 str. G6191 Brucella melitensis bv. 1 str. G6191 Brucella melitensis G8755 Brucella melitensis G8755 Brucella melitensis E8127 Brucella melitensis E8127 Brucella suis bv. 1 str. F1277 Brucella suis bv. 1 str. F1277 Brucella suis bv. 1 str. F1183 Brucella suis bv. 1 str. F1183 Brucella suis bv. 1 str. F1651 Brucella suis bv. 1 str. F1651 Brucella suis bv. 1 str. G9049 Brucella suis bv. 1 str. G9049 Brucella suis bv. 1 str. G8756 Brucella suis bv. 1 str. G8756 Brucella melitensis ATCC 23457 Brucella melitensis ATCC 23457 Brucella melitensis str. ATCC 23457 Brucella melitensis strain ATCC 23457 Brucella microti CCM 4915 Brucella microti CCM 4915 Brucella microti str. CCM 4915 Brucella microti strain CCM 4915 Brucella abortus NCTC 8038 Brucella abortus NCTC 8038 Brucella abortus str. NCTC 8038 Brucella abortus strain NCTC 8038 uncultured Brucella sp. uncultured Brucella sp. Brucella sp. QQDP515 Brucella sp. QQDP515 Brucella ceti str. Cudo Brucella ceti str. Cudo Brucella ceti strain Cudo Eumetazoa Eumetazoa Brucella sp. A4/I Brucella sp. A4/I Brucella abortus str. 2308 A Brucella abortus 2308 A Brucella abortus str. 2308 A Brucella abortus strain 2308 A Brucella suis 1-138#1108 Brucella suis 1-138#1108 Brucella suis 2367#1072 Brucella suis 2367#1072 Brucella suis F2355 Brucella suis F2355 Brucella suis bv. 1 str. F4390 Brucella suis bv. 1 str. F4390 Brucella suis bv. 1 str. H0134 Brucella suis bv. 1 str. H0134 Brucella abortus 2045#1007 Brucella abortus 2045#1007 Brucella abortus 2052#1012 Brucella abortus 2052#1012 Brucella abortus bv. 2 Brucella abortus biovar 2 Brucella abortus bv. 2 Brucella abortus bv. 2 str. D9606470 Brucella abortus bv. 2 str. D9606470 Brucella abortus bv. 3 str. G9295 Brucella abortus bv. 3 str. G9295 Brucella abortus bv. 4 Brucella abortus biovar 4 Brucella abortus bv. 4 Brucella abortus bv. 4 str. H1090 Brucella abortus bv. 4 str. H1090 Brucella melitensis bv. 1 Brucella melitensis biovar 1 Brucella melitensis bv. 1 Brucella melitensis bv. 1 str. H0877 Brucella melitensis bv. 1 str. H0877 Brucella melitensis G6605 Brucella melitensis G6605 Brucella melitensis bv. 3 Brucella melitensis biovar 3 Brucella melitensis bv. 3 Brucella melitensis bv. 3 str. G9248 Brucella melitensis bv. 3 str. G9248 Brucella melitensis bv. 3 str. G9319 Brucella melitensis bv. 3 str. G9319 Brucella melitensis H1992 Brucella melitensis H1992 Brucella melitensis bv. 3 str. K26 Brucella melitensis bv. 3 str. K26 Brucella suis bv. 1 Brucella suis biovar 1 Brucella suis bv. 1 Brucella melitensis bv. 2 Brucella melitensis biovar 2 Brucella melitensis bv. 2 Brucella suis bv. 2 Brucella suis biovar 2 Brucella suis bv. 2 Brucella sp. BD-23 Brucella sp. BD-23 Brucella sp. FXY47 Brucella sp. FXY47 Brucella sp. NF 2653 Brucella sp. NF 2653 Brucella sp. BO2 Brucella sp. BO2 Brucella sp. B202R Brucella sp. B202R Brucella melitensis M5-90 Brucella melitensis M5-90 Brucella melitensis str. M5-90 Brucella melitensis strain M5-90 Brucella sp. BDUEBTVRMK11 Brucella sp. BDUEBTVRMK11 Brucella sp. PBCC11 Brucella sp. PBCC11 Chordata Chordata chordates Vertebrata <Metazoa> Vertebrata Vertebrata <Metazoa> vertebrates Gnathostomata <vertebrate> Gnathostomata Gnathostomata <vertebrate> jawed vertebrates Brucella sp. IFC_YC15 Brucella sp. IFC_YC15 Brucella sp. M2357/93 Brucella sp. M2357/93 Sarcopterygii Sarcopterygii Brucella sp. BS33 Brucella sp. BS33 Brucella sp. BS26 Brucella sp. BS26 Mus <mouse, subgenus> Mus Mus <mouse, subgenus> environmental samples <Brucella> environmental samples environmental samples <Brucella> uncultured bacterium SY5-6 uncultured bacterium SY5-6 Craniata <chordata> Craniata Craniata <chordata> Cetartiodactyla Cetartiodactyla whales, hippos, ruminants, pigs, camels etc. Eutheria Eutheria eutherian mammals placental mammals placentals Brucella melitensis M28 Brucella melitensis M28 Brucella melitensis str. M28 Brucella melitensis strain M28 Primates Primates primate Catarrhini Catarrhini Cercopithecidae Cercopithecidae Old World monkeys monkey monkeys Cercopithecinae Cercopithecinae Chlorocebus aethiops African green monkey African green monkeys Chlorocebus aethiops green monkey grivet savanah monkey vervet monkey Hominidae Hominidae great apes Homo Homo Homo sapiens Homo sapiens human man Canidae Canidae dog, coyote, wolf, fox Canis Canis Canis lupus Canis lupus gray wolf grey wolf Canis lupus familiaris Canis lupus familiaris dog dogs Perissodactyla Perissodactyla odd-toed ungulates Equidae Equidae horses Equus Equus Equus caballus Equus caballus domestic horse equine horse Brucella sp. F60 Brucella sp. F60 Brucella sp. F965 Brucella sp. F965 Suidae Suidae boars pigs Sus Sus Sus scrofa Sus scrofa pig pigs swine wild boar Ruminantia Ruminantia Bovidae Bovidae Bos Bos oxen, cattle Bos taurus Bos taurus bovine cattle cow domestic cattle domestic cow Capra Capra Capra hircus Capra hircus domestic goat goat goats Ovis Ovis Ovis aries Ovis aries domestic sheep lambs sheep wild sheep Caprinae Caprinae Rodentia Rodentia rodents planned process A processual entity that realizes a plan which is the concretization of a plan specification. planned process processed material Is a material entity that is created or changed during material processing. processed material material processing A planned process which results in physical changes in a specified input material material processing material transformation specimen role a role borne by a material entity that is gained during a specimen collection process and that can be realized by use of the specimen in an investigation specimen role primer role a complementary nucleotide probe role which inheres in nucleic acid molecular entity and is realized by the use of the entity bearing the role to initiate chain elongation. OBI will change the difinition. primer role PCR product PCR product is double stranded DNA that is the specified output of a polymerase chain reaction polymerase chain reaction PCR PCR is the process in which a DNA polymerase is used to amplify a piece of DNA by in vitro enzymatic replication. As PCR progresses, the DNA thus generated is itself used as a template for replication. This sets in motion a chain reaction in which the DNA template is exponentially amplified. polymerase chain reaction material transformation objective an objective specifiction that creates an specific output object from input materials. artifact creation objective material transformation objective sequence data sequence data organism 10/21/09: This is a placeholder term, that should ideally be imported from the NCBI taxonomy, but the high level hierarchy there does not suit our needs (includes plasmids and 'other organisms') GROUP: OBI Biomaterial Branch An organism is material entity that is an individual living system, such as animal, plant, bacteria or virus, that is capable of replicating or reproducing, growth and maintenance in the right environment. An organism may be unicellular or made up, like humans, of many billions of cells divided into specialized tissues and organs. OBI A material entity that is an individual living system, such as animal, plant, bacteria or virus, that is capable of replicating or reproducing, growth and maintenance in the right environment. An organism may be unicellular or made up, like humans, of many billions of cells divided into specialized tissues and organs. WEB: http://en.wikipedia.org/wiki/Organism animal fungus organism plant virus specimen A material entity that has the specimen role. specimen enzymatic amplification enzymatic amplification the use of enzymes to increase the number of molecules of a biomaterial antigen antigen is a material entity that has the antigen role genome Book: Eugene Nester, Denise Anderson, C. Evans Roberts, Jr., Microbiology (Companion Site): A Human Perspective, 7th Edition. Mcgraw Hill, October 18, 2011. ISBN-13: 978-0073375311 A genome is a material entity that represents the entirety of an organism's hereditary information. The genome includes both the genes and the non-coding sequences of the DNA and RNA. Oliver He WEB: http://en.wikipedia.org/wiki/Genome gene A gene is a material entity that represents the entire DNA sequence required for synthesis of a functional protein or RNA molecule. Oliver He WEB: http://www.ncbi.nlm.nih.gov/books/NBK21640/ In addition to the coding regions (exons), a gene includes transcription-control regions and sometimes introns. Although the majority of genes encode proteins, some encode tRNAs, rRNAs, and other types of RNA. gene disposition Yongqun He a disposition that a gene can be used as a blueprint for generating a new form of product such as protein. WEB: http://www.ncbi.nlm.nih.gov/IEB/ToolBox/CPP_DOC/lxr/source/src/objects/entrezgene/entrezgene.asn YH: According to NCBI Gene project, there are two gene types: unknown (0) , tRNA (1) , rRNA (2) , snRNA (3) , scRNA (4) , snoRNA (5) , protein-coding (6) , pseudo (7) , transposon (8) , miscRNA (9) , ncRNA (10) , other (255). Therefore, we have generated corresponding gene dispositions. Note that we don't use the term "gene type" here to differentiate the meanings of "type" and "disposition". protein-coding gene disposition a gene disposition that a gene can be used as a blueprint for generating a protein (i.e., a gene encodes for a protein). WEB: http://www.ncbi.nlm.nih.gov/IEB/ToolBox/CPP_DOC/lxr/source/src/objects/entrezgene/entrezgene.asn Yongqun He pseudo gene disposition Yongqun He a gene disposition that represents the disposition of gene being "pseudo", i.e., the gene is a pseudogene. WEB: http://www.ncbi.nlm.nih.gov/IEB/ToolBox/CPP_DOC/lxr/source/src/objects/entrezgene/entrezgene.asn other gene disposition Yongqun He WEB: http://www.ncbi.nlm.nih.gov/IEB/ToolBox/CPP_DOC/lxr/source/src/objects/entrezgene/entrezgene.asn Note: The other gene disposition originates from automated generation using terms imported from the NCBI Gene resource (http://www.ncbi.nlm.nih.gov/books/NBK3841/ ). However the use of such an information-related term is not fully compliant with the Foundry Principles. Before we can find a better solution, we will for now keep them in the OGG. a gene disposition that is "other", i.e., the gene is for a gene product that is not listed for another other gene type. genome of Bacteria 2 The genome of an organism of Bacteria Yue Liu, Bin Zhao, Oliver He genome of Brucella 234 The genome of an organism of Brucella Yue Liu, Bin Zhao, Oliver He genome of Brucella suis 1330 204722 The genome of an organism of Brucella suis 1330 Yue Liu, Bin Zhao, Oliver He genome of Brucella melitensis bv. 1 str. 16M 224914 The genome of an organism of Brucella melitensis bv. 1 str. 16M Yue Liu, Bin Zhao, Oliver He genome of Brucella melitensis biovar Abortus 2308 359391 The genome of an organism of Brucella melitensis biovar Abortus 2308 Yue Liu, Bin Zhao, Oliver He gene of Bacteria 2 A gene of an organism of Bacteria Yue Liu, Bin Zhao, Oliver He gene of Brucella 234 A gene of an organism of Brucella Yue Liu, Bin Zhao, Oliver He gene of Brucella suis 1330 204722 A gene of an organism of Brucella suis 1330 Yue Liu, Bin Zhao, Oliver He gene of Brucella melitensis bv. 1 str. 16M 224914 A gene of an organism of Brucella melitensis bv. 1 str. 16M Yue Liu, Bin Zhao, Oliver He gene of Brucella melitensis biovar Abortus 2308 359391 A gene of an organism of Brucella melitensis biovar Abortus 2308 Yue Liu, Bin Zhao, Oliver He protein-coding gene of Brucella suis 1330 204722 A gene of Brucella suis 1330 that has a protein-coding gene disposition Bin Zhao, Oliver He protein-coding gene of Brucella melitensis bv. 1 str. 16M 224914 A gene of Brucella melitensis bv. 1 str. 16M that has a protein-coding gene disposition Bin Zhao, Oliver He protein-coding gene of Brucella melitensis biovar Abortus 2308 359391 A gene of Brucella melitensis biovar Abortus 2308 that has a protein-coding gene disposition Bin Zhao, Oliver He pseudo gene of Brucella suis 1330 204722 A gene of Brucella suis 1330 that has a pseudo gene disposition Bin Zhao, Oliver He pseudo gene of Brucella melitensis biovar Abortus 2308 359391 A gene of Brucella melitensis biovar Abortus 2308 that has a pseudo gene disposition Bin Zhao, Oliver He gene of Brucella suis 1330 with other gene disposition 204722 A gene of Brucella suis 1330 that has a other gene disposition Bin Zhao, Oliver He BRA0005 1164441 20140222 204722 BRA0005 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribokinase BRA0037 1164473 20140222 204722 BRA0037 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene magnesium ion-transporting ATPase E1-E2 family protein protein-coding BRA0041 1164477 20140215 204722 BRA0041 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor histidine kinase gltD 1164492 20140405 204722 BRA0055 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutamate synthase subunit beta protein-coding BRA0059 1164496 20140405 204722 BRA0059 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122; 16730027 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB11 BRA0060 1164497 20140222 204722 BRA0060 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122; 16648257; 21763312 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB10 BRA0061 1164498 20140222 204722 BRA0061 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB9 BRA0062 1164499 20140222 204722 BRA0062 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122; 15764702; 16648257; 21763312 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB8 BRA0064 1164501 20130611 204722 BRA0064 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB6 BRA0065 1164502 20140406 204722 BRA0065 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB5 BRA0066 1164503 20140222 204722 BRA0066 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122; 16648257 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB4 BRA0067 1164504 20130611 204722 BRA0067 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB3 BRA0068 1164505 20140406 204722 BRA0068 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB2 BRA0069 1164506 20140222 204722 BRA0069 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB1 hemH 1164513 20140405 204722 BRA0076 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene ferrochelatase protein-coding omp10 1164514 20130611 204722 BRA0077 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene lipoprotein Omp10 protein-coding gnd 1164548 20140405 204722 6-phosphogluconate dehydrogenase BRA0111 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BRA0119 1164556 20130611 204722 BRA0119 Bin Zhao, Yue Liu, Oliver He II LuxR family transcriptional regulator NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BRA0135 1164572 20140217 204722 BRA0135 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycosyl transferase group 2 family protein protein-coding BRA0146 1164583 20130611 204722 BRA0146 Bin Zhao, Yue Liu, Oliver He DeoR family transcriptional regulator II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding flgI 1164593 20140215 204722 BRA0156 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar basal body P-ring biosynthesis protein FlgA protein-coding BRA0177 1164614 20130611 204722 BRA0177 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding gluP 1164627 20111207 204722 BRA0190 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied WEB: http://www.ncbi.nlm.nih.gov/gene other BRA0224 1164661 20140222 204722 BRA0224 Bin Zhao, Yue Liu, Oliver He CAIB/BAIF family protein II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BRA0246 1164683 20140215 204722 BRA0246 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cytochrome c oxidase subunit III protein-coding norD 1164688 20140217 204722 BRA0251 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene norD protein protein-coding narG 1164736 20140406 204722 BRA0299 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding respiratory nitrate reductase subunit alpha nrdH 1164751 20140222 204722 BRA0314 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutaredoxin-like protein nrdH protein-coding BRA0347 1164785 20140405 204722 BRA0347 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene mannose-1-phosphate guanylyltransferase protein-coding BRA0348 1164786 20140405 204722 BRA0348 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoglucomutase protein-coding oxyR 1164792 20140405 204722 BRA0354 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transcriptional regulator OxyR xfp 1164823 20140222 204722 BRA0385 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoketolase protein-coding glpK 1164881 20140322 204722 BRA0443 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol kinase protein-coding BRA0467 1164905 20140217 204722 BRA0467 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding taurine ABC transporter permease cydD 1164946 20140222 204722 ABC transporter ATP-binding protein CydD BRA0508 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BRA0509 1164947 20140217 204722 ABC transporter ATP-binding/permease BRA0509 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding cydB 1164949 20140329 204722 BRA0511 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cytochrome d ubiquinol oxidase subunit II protein-coding BRA0568 1165007 20140215 204722 ABC transporter permease BRA0568 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pcs 1165011 20140215 204722 BRA0572 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphatidylcholine synthase protein-coding BRA0598 1165038 20140405 204722 BRA0598 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene acyl-CoA dehydrogenase protein-coding pyrB 1165039 20140329 204722 BRA0599 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene aspartate carbamoyltransferase protein-coding divK 1165052 20130611 204722 BRA0612 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene polar differentiation response regulator protein-coding ugpB 1165097 20140215 204722 BRA0655 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol-3-phosphate ABC transporter periplasmic glycerol-3-phosphate-binding protein protein-coding ugpA 1165098 20140222 204722 BRA0656 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol-3-phosphate ABC transporter permease protein-coding BRA0692 1165134 20130831 204722 BRA0692 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sugar ABC transporter permease BRA0700 1165142 20130611 204722 BRA0700 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene iron ABC transporter substrate-binding protein protein-coding sodC 1165145 20140215 204722 BRA0703 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding superoxide dismutase, Cu-Zn BRA0712 1165154 20140222 204722 BRA0712 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 SIS domain-containing protein WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding gcvP 1165167 20140405 204722 BRA0725 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycine dehydrogenase protein-coding gcvT 1165169 20140405 204722 BRA0727 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycine cleavage system aminomethyltransferase T protein-coding xseA 1165206 20130611 204722 BRA0764 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene exodeoxyribonuclease VII large subunit protein-coding zwf 1165220 20140406 204722 BRA0778 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glucose-6-phosphate 1-dehydrogenase protein-coding BRA0804 1165246 20140222 204722 BRA0804 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nickel ABC transporter nickel-binding protein protein-coding BRA0806 1165248 20130611 204722 BRA0806 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 UxaA family hydrolase WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding eryB 1165308 20140406 204722 BRA0865 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol-3-phosphate dehydrogenase protein-coding eryC 1165309 20140406 204722 BRA0866 Bin Zhao, Yue Liu, Oliver He D-erythrulose-1-phosphate dehydrogenase II NCBI-supplied PMID: 12271122; 16177356 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BRA0919 1165363 20140217 204722 BRA0919 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene molybdopterin-binding oxidoreductase protein-coding BRA0936 1165380 20140222 204722 BRA0936 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sugar ABC transporter ATP-binding protein BRA0947 1165391 20130611 204722 BRA0947 Bin Zhao, Yue Liu, Oliver He D-aminopeptidase II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BRA0987 1165431 20140215 204722 BRA0987 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cobalamin synthesis protein/P47K family protein protein-coding BRA1012 1165456 20140222 204722 ABC transporter periplasmic substrate-binding protein BRA1012 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding znuA 1165575 20140222 204722 BRA1122 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding zinc ABC transporter periplasmic zinc-binding protein znuC 1165576 20140406 204722 BRA1123 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding zinc ABC transporter ATP-binding protein flgE 1165592 20140406 204722 BRA1139 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar hook protein FlgE protein-coding motB 1165597 20140405 204722 BRA1144 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar motor protein MotB protein-coding fliF 1165599 20140215 204722 BRA1146 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar MS-ring protein protein-coding rpsA 1165684 20140222 204722 30S ribosomal protein S1 BR0027 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pheA 1165694 20140405 204722 BR0037 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene prephenate dehydratase protein-coding pgm 1165715 20140405 204722 BR0058 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoglucomutase protein-coding ilvD 1165756 20140405 204722 BR0099 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroxy-acid dehydratase protein-coding BR0111 1165768 20140222 204722 BR0111 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cyclic beta 1-2 glucan synthetase protein-coding BR0144 1165801 20140222 204722 BR0144 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PII uridylyl-transferase PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding cysI 1165838 20140405 204722 BR0181 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sulfite reductase (NADPH) hemoprotein subunit beta metH 1165845 20140406 204722 B12-dependent methionine synthase BR0188 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR0238 1165896 20140222 204722 BR0238 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sugar ABC transporter ATP-binding protein hisD 1165911 20140406 204722 BR0252 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122; 22196018 WEB: http://www.ncbi.nlm.nih.gov/gene histidinol dehydrogenase protein-coding pgi 1165946 20140406 204722 BR0285 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glucose-6-phosphate isomerase protein-coding pyrD 1165972 20140406 204722 BR0311 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroorotate dehydrogenase 2 protein-coding BR0316 1165977 20140406 204722 BR0316 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor histidine kinase/response regulator bacA 1166033 20130611 204722 BR0372 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transport protein purD 1166075 20140405 204722 BR0414 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylamine--glycine ligase protein-coding aroC 1166089 20140405 204722 BR0428 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene chorismate synthase protein-coding BR0442 1166103 20140215 204722 ABC transporter ATP-binding/permease BR0442 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding purF 1166107 20140405 204722 BR0446 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene amidophosphoribosyltransferase protein-coding BR0465 1166126 20140217 204722 BR0465 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding tldD protein thrC 1166145 20140405 204722 BR0484 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding threonine synthase BR0496 1166157 20140215 204722 BR0496 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding twin-arginine translocation pathway signal sequence domain-containing protein BR0511 1166172 20140222 204722 BR0511 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycosyl transferase group 4 family protein protein-coding wbkB 1166180 20130611 204722 BR0518 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding wbkB protein rfbD 1166182 20140215 204722 BR0520 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied O-antigen export system permease RfbD PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR0521 1166183 20140215 204722 BR0521 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene perosamine synthase protein-coding gmd 1166184 20140406 204722 BR0522 Bin Zhao, Yue Liu, Oliver He GDP-mannose 4,6-dehydratase I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR0529 1166191 20140215 204722 BR0529 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene mannosyltransferase protein-coding BR0537 1166199 20140405 204722 BR0537 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphomannomutase protein-coding BR0540 1166202 20140222 204722 BR0540 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene group 1 glycosyl transferase protein-coding BR0604 1166266 20140222 204722 BR0604 Bin Zhao, Yue Liu, Oliver He DNA-binding response regulator I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR0605 1166267 20130611 204722 BR0605 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor histidine kinase BR0611 1166273 20130611 204722 BR0611 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding serine protease BR0615 1166277 20140222 204722 BR0615 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding pepN 1166279 20140215 204722 BR0617 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene aminopeptidase protein-coding BR0652 1166315 20140222 204722 BR0652 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 RelA/SpoT family protein WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding omp25 1166364 20140215 204722 BR0701 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122; 17635859 WEB: http://www.ncbi.nlm.nih.gov/gene outer-membrane protein Omp25 protein-coding purN 1166372 20140405 204722 BR0709 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylglycinamide formyltransferase protein-coding purM 1166373 20140405 204722 BR0710 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylaminoimidazole synthetase protein-coding BR0715 1166378 20140406 204722 BR0715 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene epimerase protein-coding glyA 1166430 20140405 204722 BR0765 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding serine hydroxymethyltransferase purL 1166505 20140405 204722 BR0837 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylformylglycinamidine synthase II protein-coding tig 1166567 20140406 204722 BR0898 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding trigger factor BR0909 1166578 20140406 204722 BR0909 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BR0915 1166584 20140406 204722 BR0915 Bin Zhao, Yue Liu, Oliver He I N-acetylmuramoyl-L-alanine amidase NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR0930 1166599 20140329 204722 BR0930 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cysteine desulfurase protein-coding BR0933 1166602 20130611 204722 BR0933 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BR0955 1166625 20140222 204722 BR0955 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene amino acid ABC transporter substrate-binding protein protein-coding BR0982 1166655 20140222 204722 BR0982 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene group 1 glycosyl transferase protein-coding glnA 1166677 20140405 204722 BR1004 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutamine synthetase protein-coding BR1053 1166727 20140406 204722 BR1053 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cysteine synthase A protein-coding BR1084 1166760 20140215 204722 BR1084 Bin Zhao, Yue Liu, Oliver He CAIB/BAIF family protein I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding uvrA 1166780 20140222 204722 BR1104 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene excinuclease ABC subunit A protein-coding lon 1166782 20140222 204722 ATP-dependent protease La BR1106 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding hfq 1166787 20130611 204722 BR1111 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 RNA-binding protein Hfq WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ntrY 1166792 20130611 204722 BR1116 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nitrogen regulation protein NtrY protein-coding ntrC 1166793 20140222 204722 BR1117 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nitrogen regulation protein NtrC protein-coding BR1139 1166815 20140222 204722 BR1139 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding rotamase uppS 1166834 20140315 204722 BR1158 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding undecaprenyl pyrophosphate synthase recA 1166878 20140406 204722 BR1202 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding recombinase A rpoA 1166885 20140329 204722 BR1209 Bin Zhao, Yue Liu, Oliver He DNA-directed RNA polymerase subunit alpha I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding gloA 1166947 20140215 204722 BR1268 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene lactoylglutathione lyase protein-coding cobB 1166977 20140301 204722 BR1296 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cobyrinic acid a,c-diamide synthase protein-coding BR1378 1167060 20130611 204722 BR1378 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene class I aminotransferase protein-coding ilvC 1167062 20140405 204722 BR1380 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene ketol-acid reductoisomerase protein-coding miaA 1167072 20140329 204722 BR1390 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding tRNA delta(2)-isopentenylpyrophosphate transferase serB 1167073 20140406 204722 BR1391 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoserine phosphatase protein-coding pncA 1167146 20140405 204722 BR1464 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pyrazinamidase/nicotinamidase BR1465 1167147 20130611 204722 BR1465 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding aspC 1167178 20140406 204722 BR1495 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene aspartate aminotransferase protein-coding BR1498 1167181 20140222 204722 BR1498 Bin Zhao, Yue Liu, Oliver He I LysR family transcriptional regulator NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pth 1167219 20140406 204722 BR1536 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene peptidyl-tRNA hydrolase protein-coding leuA 1167249 2-isopropylmalate synthase 20140405 204722 BR1566 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR1642 1167334 20140217 204722 BR1642 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene disulfide bond formation protein B protein-coding BR1646 1167338 20140222 204722 BR1646 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene base-excision DNA repair protein protein-coding BR1671 1167364 20140222 204722 BR1671 Bin Zhao, Yue Liu, Oliver He HlyD family secretion protein I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding dut 1167368 20140405 204722 BR1675 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene deoxyuridine 5'-triphosphate nucleotidohydrolase protein-coding BR1676 1167369 20140222 204722 AsnC family transcriptional regulator BR1676 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding purE 1167437 20140405 204722 BR1744 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylaminoimidazole carboxylase, catalytic subunit protein-coding pyc 1167474 20140405 204722 BR1781 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pyruvate carboxylase BR1791 1167484 20140215 204722 BR1791 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene branched-chain amino acid ABC transporter permease protein-coding purH 1167509 20140405 204722 BR1816 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase protein-coding leuC 1167606 20140405 204722 BR1906 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene isopropylmalate isomerase large subunit protein-coding rplS 1167607 20130611 204722 50S ribosomal protein L19 BR1907 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding omp19 1167630 20140406 204722 BR1930 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene lipoprotein Omp19 protein-coding cysK 1167668 20111205 204722 BR1967 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied WEB: http://www.ncbi.nlm.nih.gov/gene pseudo pseudo lysA 1167684 20140405 204722 BR1983 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene diaminopimelate decarboxylase protein-coding hpt 1167686 20140405 204722 BR1985 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypoxanthine-guanine phosphoribosyltransferase protein-coding hisC 1167688 20140405 204722 BR1987 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene histidinol-phosphate aminotransferase protein-coding hisF 1167788 20140405 204722 BR2085 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene imidazole glycerol phosphate synthase subunit HisF protein-coding BR2090 1167793 20140222 204722 BR2090 Bin Zhao, Yue Liu, Oliver He DNA-binding response regulator BvrR I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BR2091 1167794 20140215 204722 BR2091 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor histidine kinase BvrS dnaK 1167828 20140215 204722 BR2125 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene molecular chaperone DnaK protein-coding pmtA 1167830 20140406 204722 BR2127 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phospholipid N-methyltransferase protein-coding mutM 1167886 20140222 204722 BR2183 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene formamidopyrimidine-DNA glycosylase protein-coding BMEI0066 1195778 20140217 224914 BMEI0066 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122; 19742243 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding two component response regulator BMEI0082 1195794 20140329 224914 BMEI0082 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypoxanthine-guanine phosphoribosyltransferase protein-coding BMEI0084 1195796 20140405 224914 BMEI0084 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene diaminopimelate decarboxylase protein-coding BMEI0085 1195797 20140222 224914 BMEI0085 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI0135 1195847 20140406 224914 BMEI0135 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene outer membrane lipoprotein protein-coding rplS 1195868 20130611 224914 50S ribosomal protein L19 BMEI0156 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0157 1195869 20140405 224914 BMEI0157 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene isopropylmalate isomerase large subunit protein-coding BMEI0169 1195881 20140222 224914 BMEI0169 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0190 1195902 20140217 224914 BMEI0190 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoenolpyruvate-protein phosphotransferase PTSP protein-coding purH 1195945 20140405 224914 BMEI0233 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase protein-coding BMEI0258 1195970 20140406 224914 BMEI0258 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene high-affinity branched-chain amino acid transport system permease livH protein-coding BMEI0266 1195978 20140405 224914 BMEI0266 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pyruvate carboxylase BMEI0267 1195979 20140217 224914 BMEI0267 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI0275 1195987 20130518 224914 ATP-dependent DNA helicase BMEI0275 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0296 1196007 20140405 224914 BMEI0296 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylaminoimidazole carboxylase catalytic subunit protein-coding BMEI0305 1196016 20140215 224914 BMEI0305 Bin Zhao, Yue Liu, Oliver He DeoR family transcriptional regulator I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0320 1196031 20140217 224914 BMEI0320 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0357 1196068 20140217 224914 AsnC family transcriptional regulator BMEI0357 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding dut 1196069 20140329 224914 BMEI0358 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene deoxyuridine 5'-triphosphate nucleotidohydrolase protein-coding BMEI0359 1196070 20140217 224914 BMEI0359 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene periplasmic protein of efflux system protein-coding BMEI0382 1196093 20140222 224914 BMEI0382 Bin Zhao, Yue Liu, Oliver He DNA-3-methyladenine glycosidase I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0384 1196095 20140215 224914 BMEI0384 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene disulfide bond formation protein B protein-coding BMEI0430 1196141 20140406 224914 BMEI0430 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nodulation protein NOLR protein-coding BMEI0433 1196144 20140329 224914 BMEI0433 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene periplasmic dipeptide transport protein protein-coding BMEI0451 1196162 2-isopropylmalate synthase 20140405 224914 BMEI0451 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0455 1196166 20140215 224914 BMEI0455 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutathione S-transferase protein-coding BMEI0480 1196191 20140406 224914 BMEI0480 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene peptidyl-tRNA hydrolase protein-coding BMEI0509 1196220 20130526 224914 BMEI0509 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene lipopolysaccharide core biosynthesis mannosyltransferase LPCC protein-coding BMEI0512 1196223 20140405 224914 BMEI0512 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding thioredoxin reductase BMEI0513 1196224 20140222 224914 BMEI0513 Bin Zhao, Yue Liu, Oliver He I LysR family transcriptional regulator NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0516 1196227 20140405 224914 BMEI0516 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene aspartate aminotransferase protein-coding BMEI0526 1196237 20140406 224914 BMEI0526 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene carbamoyl phosphate synthase small subunit protein-coding BMEI0536 1196247 20130611 224914 BMEI0536 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene immunogenic protein protein-coding BMEI0545 1196256 20130518 224914 BMEI0545 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI0605 1196316 20140217 224914 BMEI0605 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene bicyclomycin resistance protein protein-coding BMEI0615 1196326 20140405 224914 BMEI0615 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoserine phosphatase protein-coding miaA 1196327 20140405 224914 BMEI0616 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding tRNA delta(2)-isopentenylpyrophosphate transferase BMEI0617 1196328 20140405 224914 BMEI0617 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene acetolactate synthase 3 catalytic subunit protein-coding BMEI0624 1196335 20140405 224914 BMEI0624 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene ketol-acid reductoisomerase protein-coding BMEI0626 1196337 20130518 224914 BMEI0626 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0671 1196382 20130526 224914 BMEI0671 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene integral membrane protein / hemolysin protein-coding BMEI0705 1196416 20140405 224914 BMEI0705 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cobyrinic acid a,c-diamide synthase protein-coding BMEI0725 1196436 20140405 224914 BMEI0725 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene homoserine dehydrogenase protein-coding BMEI0730 1196441 20140222 224914 BMEI0730 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene lactoylglutathione lyase protein-coding BMEI0781 1196492 20140405 224914 BMEI0781 Bin Zhao, Yue Liu, Oliver He DNA-directed RNA polymerase subunit alpha I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding recA 1196498 20140405 224914 BMEI0787 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding recombinase A BMEI0827 1196538 20140329 224914 BMEI0827 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding undecaprenyl pyrophosphate synthase BMEI0845 1196556 20140215 224914 BMEI0845 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene peptidyl-prolyl cis-trans isomerase D protein-coding BMEI0867 1196578 20140406 224914 BMEI0867 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nitrogen regulation protein NTRY protein-coding hfq 1196583 20130611 224914 BMEI0872 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 RNA-binding protein Hfq WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0876 1196587 20130518 224914 ATP-dependent protease LA BMEI0876 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding uvrA 1196589 20140215 224914 BMEI0878 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene excinuclease ABC subunit A protein-coding BMEI0881 1196592 20140222 224914 BMEI0881 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI0898 1196609 20140222 224914 BMEI0898 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene acyl-CoA transferase protein-coding BMEI0933 1196644 20140405 224914 BMEI0933 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cysteine synthase A protein-coding BMEI0979 1196690 20140405 224914 BMEI0979 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutamine synthetase protein-coding BMEI0997 1196708 20140222 224914 BMEI0997 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene mannosyltransferase protein-coding moaA 1196730 20140322 224914 BMEI1019 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene molybdenum cofactor biosynthesis protein A protein-coding BMEI1040 1196751 20140222 224914 ABC transporter ATP-binding protein BMEI1040 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1043 1196754 20140322 224914 BMEI1043 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied NifS protein PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1056 1196767 20140215 224914 BMEI1056 Bin Zhao, Yue Liu, Oliver He I N-acetylmuramoyl-L-alanine amidase NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1060 1196771 20140215 224914 BMEI1060 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding tig 1196780 20140222 224914 BMEI1069 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding trigger factor BMEI1104 1196815 20140215 224914 BMEI1104 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene arginine/ornithine-binding periplasmic protein precursor protein-coding BMEI1116 1196827 20140405 224914 BMEI1116 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribulose-phosphate 3-epimerase BMEI1127 1196838 20140329 224914 BMEI1127 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylformylglycinamidine synthase II protein-coding BMEI1192 1196903 20140406 224914 BMEI1192 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding serine hydroxymethyltransferase BMEI1229 1196940 20130611 224914 BMEI1229 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene exonuclease protein-coding BMEI1237 1196948 20140405 224914 BMEI1237 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 UDP-glucose 4-epimerase WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1240 1196951 20140329 224914 BMEI1240 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylaminoimidazole synthetase protein-coding purN 1196952 20140405 224914 BMEI1241 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylglycinamide formyltransferase protein-coding BMEI1249 1196960 20140405 224914 BMEI1249 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1258 1196969 20140215 224914 ABC transporter ATP-binding protein BMEI1258 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1281 1196992 20140322 224914 BMEI1281 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroorotase protein-coding BMEI1296 1197007 20140215 224914 BMEI1296 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase protein-coding BMEI1326 1197037 20140406 224914 BMEI1326 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1330 1197041 20140222 224914 BMEI1330 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protease Do protein-coding BMEI1336 1197047 20140222 224914 BMEI1336 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor protein PHOQ BMEI1337 1197048 20140405 224914 BMEI1337 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transcriptional regulatory protein PhoP BMEI1339 1197050 20120912 224914 BMEI1339 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1361 1197072 20120912 224914 BMEI1361 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1393 1197104 20140222 224914 BMEI1393 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene mannosyltransferase protein-coding BMEI1396 1197107 20140405 224914 BMEI1396 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphomannomutase protein-coding BMEI1404 1197115 20140217 224914 BMEI1404 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene mannosyltransferase protein-coding BMEI1413 1197124 20140406 224914 BMEI1413 Bin Zhao, Yue Liu, Oliver He GDP-mannose 4,6-dehydratase I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1414 1197125 20140406 224914 BMEI1414 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene perosamine synthetase protein-coding BMEI1426 1197137 20140222 224914 BMEI1426 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding undecaprenyl-phosphate alpha-N-acetylglucosaminyltransferase BMEI1440 1197151 20140215 224914 BMEI1440 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding thiol:disulfide interchange protein DsbA BMEI1443 1197154 2-haloalkanoic acid dehalogenase 20140405 224914 BMEI1443 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1448 1197159 20140222 224914 BMEI1448 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene c-di-GMP phosphodiesterase A-related protein protein-coding BMEI1450 1197161 20140405 224914 BMEI1450 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding threonine synthase BMEI1468 1197179 20130526 224914 BMEI1468 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 TLDD protein WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1488 1197199 20140405 224914 BMEI1488 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene amidophosphoribosyltransferase protein-coding BMEI1498 1-deoxy-D-xylulose-5-phosphate synthase 1197209 20140405 224914 BMEI1498 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1506 1197217 20140405 224914 BMEI1506 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene chorismate synthase protein-coding BMEI1519 1197230 20140405 224914 BMEI1519 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylamine--glycine ligase protein-coding BMEI1531 1197242 20140222 224914 BMEI1531 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1553 1197264 20140222 224914 BMEI1553 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transporter BMEI1573 1197284 20140222 224914 BMEI1573 Bin Zhao, Yue Liu, Oliver He I LysR family transcriptional regulator NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1606 1197317 20140215 224914 BMEI1606 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensory transduction histidine kinase BMEI1611 1197322 20140329 224914 BMEI1611 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroorotate dehydrogenase 2 protein-coding pgi 1197347 20140405 224914 BMEI1636 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glucose-6-phosphate isomerase protein-coding BMEI1658 1197369 20130611 224914 BMEI1658 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding hisD 1197379 20140405 224914 BMEI1668 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene histidinol dehydrogenase protein-coding BMEI1713 1197424 20140215 224914 BMEI1713 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene maltose ABC transporter ATP-binding protein protein-coding BMEI1742 1197453 20130508 224914 ABC transporter ATP-binding protein BMEI1742 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding metH 1197470 20140405 224914 B12-dependent methionine synthase BMEI1759 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1766 1197477 20140405 224914 BMEI1766 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sulfite reductase (ferredoxin) BMEI1786 1197497 20140406 224914 BMEI1786 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nitrogen regulatory IIA protein protein-coding BMEI1804 1197515 20140215 224914 BMEI1804 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PII uridylyl-transferase PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1809 1197520 20140215 224914 BMEI1809 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1837 1197548 20130518 224914 BMEI1837 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cellobiose-phosphorylase protein-coding BMEI1844 1197555 20140406 224914 BMEI1844 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1848 1197559 20140405 224914 BMEI1848 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroxy-acid dehydratase protein-coding BMEI1849 1197560 20140222 224914 BMEI1849 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding thiol:disulfide interchange protein CYCY precursor BMEI1859 1197570 20130526 224914 BMEI1859 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1879 1197590 20130526 224914 BMEI1879 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEI1886 1197597 20140405 224914 BMEI1886 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoglucomutase protein-coding BMEI1902 1197613 20140215 224914 BMEI1902 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene molybdopterin biosynthesis protein protein-coding BMEI1913 1197624 20140222 224914 BMEI1913 Bin Zhao, Yue Liu, Oliver He I LysR family transcriptional regulator NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding rpsA 1197626 20140222 224914 30S ribosomal protein S1 BMEI1915 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEI1946 1197657 20140406 224914 BMEI1946 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene formamidopyrimidine-DNA glycosylase protein-coding dnaK 1197713 20140217 224914 BMEI2002 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene molecular chaperone DnaK protein-coding BMEI2035 1197746 20140217 224914 BMEI2035 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensor protein CHVG BMEI2036 1197747 20140222 224914 BMEI2036 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transcriptional regulatory protein chvI BMEI2041 1197752 20140405 224914 BMEI2041 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene imidazole glycerol phosphate synthase subunit HisF protein-coding BMEII0017 1197788 20130611 224914 BMEII0017 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene outer membrane lipoprotein protein-coding hemH 1197789 20140405 224914 BMEII0018 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene ferrochelatase protein-coding BMEII0025 1197796 20140217 224914 BMEII0025 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene attachment mediating protein VIRB1-like protein protein-coding BMEII0026 1197797 20140406 224914 BMEII0026 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 VirB2 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0027 1197798 20130611 224914 BMEII0027 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 VirB3 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0028 1197799 20140215 224914 ATPase VIRB4-like protein BMEII0028 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0029 1197800 20130611 224914 BMEII0029 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 VirB5 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0030 1197801 20140222 224914 BMEII0030 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene channel protein VIRB6-like protein protein-coding BMEII0032 1197803 20140222 224914 BMEII0032 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 VirB8 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0033 1197804 20140222 224914 BMEII0033 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene channel protein VIRB9-like protein protein-coding BMEII0034 1197805 20140222 224914 BMEII0034 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene channel protein VIRB10-like protein protein-coding BMEII0035 1197806 20130508 224914 ATPase VIRB11-like protein BMEII0035 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding gltD 1197810 20140405 224914 BMEII0039 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutamate synthase subunit beta protein-coding BMEII0040 1197811 20140405 224914 BMEII0040 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutamate synthase [NADPH] large chain protein-coding BMEII0052 1197823 20140222 224914 BMEII0052 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sensory transduction histidine kinase BMEII0056 1197827 20130526 224914 BMEII0056 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene magnesium ABC transporter ATPase protein-coding BMEII0077 1197848 20140405 224914 BMEII0077 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene isochorismate synthase protein-coding BMEII0089 1197860 20140215 224914 BMEII0089 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribokinase BMEII0116 1197887 20140215 224914 BMEII0116 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0128 1197899 20140215 224914 BMEII0128 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene hypothetical protein protein-coding BMEII0136 1197907 20130518 224914 BMEII0136 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene homoprotocatechuate 2,3-dioxygenase protein-coding BMEII0150 1197921 20140405 224914 BMEII0150 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellin protein-coding BMEII0151 1197922 20140222 224914 BMEII0151 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar M-ring protein FLIF protein-coding motB 1197925 20140329 224914 BMEII0154 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar motor protein MotB protein-coding BMEII0158 1197929 20140222 224914 BMEII0158 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding two component response regulator flgE 1197930 20140329 224914 BMEII0159 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar hook protein FlgE protein-coding BMEII0166 1197937 20140215 224914 BMEII0166 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar biosynthetic protein FlhA protein-coding BMEII0177 1197948 20140215 224914 BMEII0177 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene high-affinity zinc uptake system ATP-binding protein ZNUC protein-coding BMEII0178 1197949 20140215 224914 BMEII0178 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene high-affinity zinc uptake system protein ZNUA protein-coding engB - 1198045 20140406 224914 BMEII0274 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribosome biogenesis GTP-binding protein YsxC yihA ysxC BMEII0300 1198072 20140406 224914 BMEII0300 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribose ABC transporter ATP-binding protein BMEII0308 1198080 20140222 224914 BMEII0308 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding zinc transporter BMEII0318 1198090 20140217 224914 6-aminohexanoate-dimer hydrolase BMEII0318 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0336 1198108 20140222 224914 ABC transporter permease BMEII0336 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0350 1198122 20140406 224914 BMEII0350 Bin Zhao, Yue Liu, Oliver He D-aminopeptidase II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0361 1198133 20140222 224914 BMEII0361 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sugar transport ATP-binding protein BMEII0378 1198150 20140222 224914 BMEII0378 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene formate dehydrogenase alpha chain protein-coding BMEII0390 1198162 20130508 224914 BMEII0390 Bin Zhao, Yue Liu, Oliver He II LysR family transcriptional regulator NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0428 1198200 20140405 224914 BMEII0428 Bin Zhao, Yue Liu, Oliver He D-erythrulose 4-phosphate dehydrogenase II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0429 1198201 20140215 224914 BMEII0429 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol-3-phosphate dehydrogenase protein-coding BMEII0475 1198247 20140406 224914 BMEII0475 Bin Zhao, Yue Liu, Oliver He GntR family transcriptional regulator II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0485 1198257 20140222 224914 BMEII0485 Bin Zhao, Yue Liu, Oliver He D-galactarate dehydratase II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0487 1198259 20130611 224914 BMEII0487 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nickel-binding periplasmic protein precursor protein-coding BMEII0513 1198285 20140405 224914 BMEII0513 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glucose-6-phosphate 1-dehydrogenase protein-coding xseA 1198299 20140222 224914 BMEII0527 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene exodeoxyribonuclease VII large subunit protein-coding BMEII0570 1198342 20140329 224914 BMEII0570 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sugar phosphate isomerase/epimerase IolE BMEII0573 1198345 20140405 224914 BMEII0573 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 RPIR family transcriptional regulator WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0581 1198353 20140222 224914 BMEII0581 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding superoxide dismutase (Cu-Zn) BMEII0584 1198356 20140222 224914 BMEII0584 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene iron(III)-binding periplasmic protein precursor protein-coding BMEII0591 1198363 20140406 224914 BMEII0591 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding sugar transport system permease BMEII0624 1198396 20130611 224914 BMEII0624 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 SN-glycerol-3-phosphate transport system permease UGPA WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII0626 1198398 20130611 224914 BMEII0626 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene membrane dipeptidase protein-coding BMEII0659 1198431 20130611 224914 BMEII0659 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding two component response regulator BMEII0669 1198441 20140405 224914 BMEII0669 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroorotase protein-coding pyrB 1198442 20140405 224914 BMEII0670 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene aspartate carbamoyltransferase protein-coding BMEII0671 1198443 20140222 224914 BMEII0671 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene acyl-CoA dehydrogenase protein-coding BMEII0701 1198473 20130518 224914 BMEII0701 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribose ABC transporter permease BMEII0759 1198531 20140405 224914 BMEII0759 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene cytochrome D ubiquinol oxidase subunit II protein-coding BMEII0761 1198533 20130518 224914 BMEII0761 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transport ATP-binding protein CYDC BMEII0762 1198534 20130611 224914 BMEII0762 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transport ATP-binding protein CYDD BMEII0799 1198571 20140222 224914 BMEII0799 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nitrate transport permease NRTB protein-coding BMEII0823 1198595 20140405 224914 BMEII0823 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol kinase protein-coding BMEII0881 1198653 20140406 224914 BMEII0881 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoketolase protein-coding BMEII0899 1198671 20140405 224914 BMEII0899 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene phosphomannomutase protein-coding BMEII0900 1198672 20140405 224914 BMEII0900 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene mannose-6-phosphate isomerase protein-coding BMEII0923 1198695 20130526 224914 BMEII0923 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding spermidine/putrescine-binding periplasmic protein nrdI 1198703 20140215 224914 BMEII0931 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding ribonucleotide reductase stimulatory protein BMEII0932 1198704 20140222 224914 BMEII0932 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glutaredoxin protein-coding BMEII0935 1198707 20140215 224914 BMEII0935 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nickel resistance protein protein-coding BMEII0950 1198722 20140405 224914 BMEII0950 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene nitrate reductase alpha chain protein-coding BMEII1001 1198773 20140215 224914 BMEII1001 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene heme-copper oxidase subunit III protein-coding BMEII1037 1198809 20140222 224914 BMEII1037 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding zinc protease BMEII1045 1198817 20130511 224914 BMEII1045 Bin Zhao, Yue Liu, Oliver He HAD superfamily protein involved in N-acetyl-glucosamine catabolism II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII1053 1198825 20140215 224914 BMEII1053 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glucose/galactose transporter protein-coding BMEII1066 1198838 20140406 224914 BMEII1066 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pyruvate dehydrogenase complex repressor flgI 1198856 20140215 224914 BMEII1084 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar basal body P-ring biosynthesis protein FlgA protein-coding BMEII1093 1198865 20130611 224914 BMEII1093 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene glycerol-3-phosphate regulon repressor protein-coding BMEII1101 1198873 20140215 224914 BMEII1101 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene bactoprenol glucosyl transferase / bactoprenol apolipoprotein N-acyltransferase protein-coding BMEII1116 1198888 20130508 224914 BMEII1116 Bin Zhao, Yue Liu, Oliver He II LuxR family transcriptional regulator NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding BMEII1124 1198896 20140405 224914 6-phosphogluconate dehydrogenase BMEII1124 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 11756688; 12271122 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding metH 20140405 359391 3786978 B12-dependent methionine synthase BAB1_0188 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pgi 20140405 359391 3787092 BAB1_0316 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glucose-6-phosphate isomerase protein-coding tig 20130511 359391 3787589 BAB1_0917 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding trigger factor uvrA 20130702 359391 3787776 BAB1_1128 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene excinuclease ABC subunit A protein-coding BAB1_1355 20130511 359391 3787926 BAB1_1355 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene calcium-binding EF-hand protein-coding miaA 20140405 359391 3787973 BAB1_1409 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding tRNA delta(2)-isopentenylpyrophosphate transferase pgk 20140405 359391 3788256 BAB1_1742 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoglycerate kinase protein-coding aroC 20140405 359391 3788622 BAB1_0454 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene chorismate synthase protein-coding aspC 20140405 359391 3788626 BAB1_1514 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene aspartate aminotransferase protein-coding bacA 20121017 359391 3788635 BAB1_0402 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding transporter cysI 20140406 359391 3788677 BAB1_0181 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene nitrite/sulfite reductase ferredoxin subunit protein-coding dut 20140405 359391 3788687 BAB1_1687 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene deoxyuridine 5'-triphosphate nucleotidohydrolase protein-coding glnA 20140405 359391 3788725 BAB1_1023 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glutamine synthetase protein-coding gloA 20140217 359391 3788728 BAB1_1286 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glyoxalase/bleomycin resistance protein/dioxygenase protein-coding glyA 20140405 359391 3788734 BAB1_0787 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding serine hydroxymethyltransferase gmd 20140406 359391 3788735 BAB1_0545 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding short-chain dehydrogenase hfq 20130702 359391 3788748 BAB1_1134 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 RNA-binding protein Hfq WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding hisC 20140405 359391 3788751 BAB1_1988 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene histidinol-phosphate aminotransferase protein-coding hisD 20140405 359391 3788752 BAB1_0285 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene histidinol dehydrogenase protein-coding hisF 20140405 359391 3788754 BAB1_2086 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene imidazole glycerol phosphate synthase subunit HisF protein-coding hpt 20140405 359391 3788755 BAB1_1986 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosyltransferase protein-coding ilvD 20140405 359391 3788763 BAB1_0096 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroxy-acid dehydratase protein-coding leuA 2-isopropylmalate synthase 20140406 359391 3788771 BAB1_1583 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding leuC 20140405 359391 3788772 BAB1_1905 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene isopropylmalate isomerase large subunit protein-coding lysA 20140405 359391 3788788 BAB1_1984 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene diaminopimelate decarboxylase protein-coding manA 20111201 359391 3788792 BAB1_0562 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied WEB: http://www.ncbi.nlm.nih.gov/gene pseudo pseudo ntrC 20140222 359391 3788817 BAB1_1140 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding response regulator receiver ntrY 20130508 359391 3788818 BAB1_1139 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PAS/histidine kinase/ATPase domain-containing protein PMID: 16299333; 22582926 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding omp19 20140406 359391 3788831 BAB1_1930 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333; 18761420 WEB: http://www.ncbi.nlm.nih.gov/gene lipoprotein Omp19 protein-coding pepN 20140405 359391 3788843 BAB1_0641 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene aminopeptidase N protein-coding pgm 20140405 359391 3788847 BAB1_0055 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoglucomutase protein-coding pheA 20140329 359391 3788850 BAB1_0034 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene prephenate dehydratase protein-coding pth 20140406 359391 3788869 BAB1_1552 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene peptidyl-tRNA hydrolase protein-coding purD 20140322 359391 3788874 BAB1_0442 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylamine--glycine ligase protein-coding purF 20140405 359391 3788875 BAB1_0472 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene amidophosphoribosyltransferase protein-coding purH 20140405 359391 3788876 BAB1_1824 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase protein-coding purM 20140405 359391 3788878 BAB1_0731 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylaminoimidazole synthetase protein-coding purN 20140405 359391 3788879 BAB1_0730 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene phosphoribosylglycinamide formyltransferase protein-coding pyc 20140405 359391 3788880 BAB1_1791 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding pyruvate carboxylase pyrD 20140405 359391 3788883 BAB1_0341 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene dihydroorotate dehydrogenase 2 protein-coding recA 20140406 359391 3788897 BAB1_1224 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding recombinase A rfbD 20130508 359391 3788901 BAB1_0543 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene acriflavin ABC transporter protein-coding rplS 20130702 359391 3788922 50S ribosomal protein L19 BAB1_1906 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding rpoA 20140405 359391 3788935 BAB1_1231 Bin Zhao, Yue Liu, Oliver He DNA-directed RNA polymerase subunit alpha I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding rpsA 20130508 30S ribosomal protein S1 359391 3788939 BAB1_0025 Bin Zhao, Yue Liu, Oliver He I NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding flgE 20140406 359391 3827409 BAB2_1098 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar hook protein FlgE protein-coding motB 20140405 359391 3827414 BAB2_1103 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar motor protein MotB protein-coding ugpA 20130529 359391 3827693 BAB2_0584 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene binding-protein dependent transport system inner membrane protein protein-coding ugpB 20130529 359391 3827694 BAB2_0585 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding solute-binding family 1 protein znuA 20130702 359391 3827700 BAB2_1079 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene periplasmic solute binding protein protein-coding znuC 20130702 359391 3827702 ABC transporter ATPase BAB2_1080 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding nrdH 20140222 359391 3827703 BAB2_0891 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glutaredoxin protein-coding pyrB 20140405 359391 3827823 BAB2_0641 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene aspartate carbamoyltransferase catalytic subunit protein-coding sodC 20140215 359391 3827840 BAB2_0535 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene copper/Zinc superoxide dismutase protein-coding BAB2_0061 20140222 359391 3827898 BAB2_0061 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333; 18469100 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding virulence protein xseA 20130529 359391 3827916 BAB2_0475 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene exodeoxyribonuclease VII large subunit protein-coding narG 20140405 359391 3827924 BAB2_0904 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene nitrate reductase subunit alpha protein-coding BAB2_0064 20130529 359391 3827978 BAB2_0064 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333; 18469100 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB5 BAB2_0066 20130508 359391 3827980 BAB2_0066 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB3-like protein BAB2_0067 20140406 359391 3827981 BAB2_0067 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding type IV secretion system protein VirB2 omp10 20121228 359391 3828036 BAB2_0076 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene lipoprotein Omp10 protein-coding cydB 20140405 359391 3828142 BAB2_0727 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333; 22919638 WEB: http://www.ncbi.nlm.nih.gov/gene cytochrome bd ubiquinol oxidase subunit II protein-coding divK 20130702 359391 3828149 BAB2_0628 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding response regulator receiver flgI 20120329 359391 3828215 BAB2_0153 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied WEB: http://www.ncbi.nlm.nih.gov/gene pseudo pseudo flgI 20120329 359391 3828216 BAB2_0154 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied WEB: http://www.ncbi.nlm.nih.gov/gene pseudo pseudo fliF 20140215 359391 3828220 BAB2_1105 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene flagellar MS-ring protein protein-coding gcvP 20140405 359391 3828233 BAB2_0515 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glycine dehydrogenase protein-coding gcvT 20140405 359391 3828234 BAB2_0513 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glycine cleavage system aminomethyltransferase T protein-coding glpK 20120329 359391 3828238 BAB2_0796 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied WEB: http://www.ncbi.nlm.nih.gov/gene pseudo pseudo gltD 20140405 359391 3828240 BAB2_0054 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene glutamate synthase subunit beta protein-coding gnd 20140405 359391 3828241 6-phosphogluconate dehydrogenase BAB2_0109 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene protein-coding hemH 20140322 359391 3828247 BAB2_0075 Bin Zhao, Yue Liu, Oliver He II NCBI-supplied PMID: 16299333 WEB: http://www.ncbi.nlm.nih.gov/gene ferrochelatase protein-coding clinical finding A representation that is either the output of a clinical history taking or a physical examination or an image finding, or some combination thereof. Albert Goldfain http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf creation date: 2010-07-19T10:18:02Z clinical history creation date: 2010-07-19T10:18:59Z A series of statements representing health-relevant qualities of a patient and of a patient's family. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain clinical picture A representation of the clinically significant bodily components and/or bodily processes of a human being that is inferred from the totality of relevant clinical findings. creation date: 2010-07-19T10:20:20Z Albert Goldfain http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf image finding creation date: 2009-06-23T10:21:10Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A representation of an image that supports an inference to an assertion about some quality of a patient. Albert Goldfain laboratory finding Albert Goldfain http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A representation of a quality of a specimen that is the output of a laboratory test and that can support an inference to an assertion about some quality of the patient. creation date: 2009-06-23T10:21:58Z preclinical finding creation date: 2009-06-23T10:22:44Z Albert Goldfain http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A representation of a quality of a patient that is (1) recorded by a clinician because the quality is hypothesized to be of clinical significance and (2) refers to qualities obtaining in the patient prior to their becoming detectable in a clinical history taking or physical examination. symptom symptom note: defined class creation date: 2010-11-18T11:02:10Z A quality of a patient that is observed by the patient and is hypothesized by the patient to be a realization of a disease. A quality of a patient that is observed by the patient or a processual entity experienced by the patient, either of which is hypothesized by the patient to be a realization of a disease. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf manifestation of a disease http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain A quality of a patient that is (a) a deviation from clinical normality that exists in virtue of the realization of a disease and (b) is observable. creation date: 2009-06-23T11:12:33Z phenotype creation date: 2010-07-19T11:13:49Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain A (combination of) quality(ies) of an organism determined by the interaction of its genetic make-up and environment that differentiates specific instances of a species from other instances of the same species. sign note: defined class A quality of a patient, a material entity that is part of a patient, or a processual entity that a patient participates in, any one of which is observed in a physical examination and is deemed by the clinician to be of clinical significance. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf creation date: 2010-11-18T11:14:36Z Albert Goldfain clinical manifestation of a disease Albert Goldfain creation date: 2009-06-23T11:15:43Z A manifestation of a disease that is detectable in a clinical history taking or physical examination. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf preclinical manifestation of a disease A manifestation of a disease that exists prior to the time at which it would be detected in a clinical history taking or physical examination, if the patient were to present to a clinician. A realization of a disease that exists prior to its becoming detectable in a clinical history taking or physical examination. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain creation date: 2009-06-23T11:16:50Z clinical phenotype Albert Goldfain creation date: 2009-06-23T11:18:05Z A clinically abnormal phenotype. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf disease phenotype creation date: 2009-06-23T11:18:39Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A clinically abnormal phenotype that is characteristic of a single disease. Albert Goldfain vital sign http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A physical sign in which a non-zero value is standardly considered to be an indication that the organism is alive. Albert Goldfain creation date: 2009-06-23T11:19:17Z predisposition to disease of type X creation date: 2009-06-23T11:20:25Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A disposition in an organism that constitutes an increased risk of the organism's subsequently developing the disease X. Albert Goldfain disease A disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism. Albert Goldfain disease creation date: 2009-06-23T11:21:20Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf homeostasis creation date: 2009-06-23T11:22:01Z Albert Goldfain genetic predisposition to disease of type X http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf creation date: 2009-06-23T11:23:07Z Albert Goldfain A predisposition to disease of type X whose physical basis is a constitutional abnormality in an organism's genome. This abnormality is the physical basis for the increased risk of acquiring the disease X. acquired genetic disease creation date: 2009-06-23T11:24:05Z A disease whose physical basis is an acquired genetic disorder. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain constitutional genetic disease http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf creation date: 2009-06-23T11:24:59Z A disease whose physical basis is a constitutional genetic disorder. Albert Goldfain abnormal homeostasis Homeostasis that is clinically abnormal for an organism of a given type and age in a given environment. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain creation date: 2009-06-23T11:26:44Z normal homeostasis Albert Goldfain Homeostasis of a type that is not clinically abnormal. creation date: 2009-06-23T11:27:28Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf configuration creation date: 2009-06-23T11:36:24Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A quality which is an spatial arrangement or distribution of a(n) independent continuant(s) across a Three Dimensional Region. Albert Goldfain pathological physical configuration Albert Goldfain A configuration which deviates in some way from a canonical configuration for a particular organism. creation date: 2009-06-23T11:36:58Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf disorder A material entity which is clinically abnormal and part of an extended organism. Disorders are the physical basis of disease. disorder creation date: 2009-06-23T11:39:44Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain epigenetic disorder creation date: 2009-06-23T11:40:27Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain A disorder whose etiology involves (1) a modification to the patient's genomic DNA which leads to alterations in the normal expression pattern of the genome, but is (2) not a change in the nucleotide sequence. genetic disorder Albert Goldfain creation date: 2009-06-23T11:41:14Z A disorder whose etiology involves an abnormality in the nucleotide sequence of an organism's genome. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf acquired genetic disorder http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A genetic disorder acquired by a single cell in an organism that leads to a population of cells within the organism bearing the disorder. Albert Goldfain creation date: 2009-06-23T11:43:09Z constitutional genetic disorder creation date: 2009-06-23T11:43:44Z Albert Goldfain A genetic disorder inherited during conception that is part of all cells in the organism. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf clinical history taking http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain An interview in which a clinician elicits a clinical history from a patient or from a third party who is reporting on behalf of the patient. creation date: 2009-06-23T11:49:16Z laboratory test creation date: 2009-06-23T11:49:49Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A measurement assay that has as input a patient-derived specimen, and as output a result that represents a quality of the specimen. Albert Goldfain physical examination creation date: 2010-07-19T11:50:18Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain A sequence of acts of observing and measuring qualities of a patient performed by a clinician; measurements may occur with and without elicitation. etiological process http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf Albert Goldfain creation date: 2009-06-23T11:53:07Z A process in an organism that leads to a subsequent disorder. bodily process Albert Goldfain creation date: 2009-06-23T11:53:49Z pathological bodily process Albert Goldfain http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A bodily process that is clinically abnormal. creation date: 2009-06-23T11:54:29Z disease course disease course The totality of all processes through which a given disease instance is realized. http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf creation date: 2009-06-23T11:55:44Z Albert Goldfain chronic disease course http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A disease course that (a) does not terminate in a return to normal homeostasis and (b) would, absent intervention, fall within abnormal homeostatic range. creation date: 2009-06-23T11:56:26Z Albert Goldfain progressive disease course creation date: 2009-06-23T11:57:09Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A disease course that (a) does not terminate in a return to normal homeostasis and (b) would, absent intervention, involve an increasing deviation from homeostasis. Albert Goldfain transient disease course creation date: 2009-06-23T11:57:44Z Albert Goldfain http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A disease course that terminates in a return to normal homeostasis. _undefined primitive term creation date: 2009-06-23T11:58:22Z Albert Goldfain clinically abnormal Albert Goldfain creation date: 2009-06-23T11:59:24Z physical basis creation date: 2009-06-23T12:00:09Z Albert Goldfain realization Albert Goldfain creation date: 2009-06-23T12:00:39Z diagnosis Albert Goldfain creation date: 2009-06-23T12:42:23Z http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf The representation of a conclusion of a diagnostic process. normal value http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf A value for a quality reported in a lab report and asserted by the testing lab or the kit manufacturer to be normal based on a statistical treatment of values from a reference population. Albert Goldfain creation date: 2009-06-26T10:31:34Z pathological formation http://ontology.buffalo.edu/bio/ISMB/ISMB_Bio-ontologies.pdf Albert Goldfain TODO: Define, relate to disorder, and place in the OGMS hierarchy. creation date: 2009-07-13T02:14:59Z pathological anatomical structure creation date: 2009-07-13T02:14:05Z http://ontology.buffalo.edu/bio/ISMB/ISMB_Bio-ontologies.pdf Albert Goldfain An anatomical structure (FMA) is pathological whenever (1) it has come into being as a result of changes in some pre-existing canonical anatomical structure, (2) through processes other than the expression of the normal complement of genes of an organism of the given type, and (3) is predisposed to have health-related consequences for the organism in question manifested by symptoms and signs. portion of pathological body substance TODO: Define, relate to disorder, and place in the OGMS hierarchy. http://ontology.buffalo.edu/bio/ISMB/ISMB_Bio-ontologies.pdf Albert Goldfain creation date: 2009-07-13T02:15:17Z pathological transformation A pathological bodily process in which a canonical anatomical structure becomes a pathological anatomical structure. creation date: 2009-07-13T02:17:07Z http://ontology.buffalo.edu/bio/ISMB/ISMB_Bio-ontologies.pdf Albert Goldfain pathological derivation http://ontology.buffalo.edu/bio/ISMB/ISMB_Bio-ontologies.pdf creation date: 2009-07-13T02:17:24Z A pathological bodily process in which matter is reorganized in such a way as to give rise to new pathological formations which take the place of entities existing earlier. Albert Goldfain pathological invasion http://ontology.buffalo.edu/bio/ISMB/ISMB_Bio-ontologies.pdf creation date: 2009-07-13T02:17:47Z Albert Goldfain TODO: Define. physical examination finding http://code.google.com/p/ogms/issues/detail?id=26 Albert Goldfain TODO: Define. creation date: 2009-11-24T04:51:11Z organism population An aggregate of organisms of the same type. http://code.google.com/p/ogms/issues/detail?id=33 Albert Goldfain creation date: 2009-11-24T04:51:11Z pain http://code.google.com/p/ogms/issues/detail?id=13 creation date: 2009-11-24T04:51:11Z Albert Goldfain TODO: Define. syndrome A pattern of signs and symptoms that typically co-occur. http://code.google.com/p/ogms/issues/detail?id=32 Albert Goldfain creation date: 2009-11-24T04:51:11Z extended organism Albert Goldfain An object aggregate consisting of an organism and all material entities located within the organism, overlapping the organism, or occupying sites formed in part by the organism. creation date: 2010-01-25T04:51:11Z http://code.google.com/p/ogms/issues/detail?id=3 extended organism patient symptom report creation date: 2010-01-25T04:51:11Z Albert Goldfain A communication from a patient about something they perceive as being abnormal about their body or life. http://code.google.com/p/ogms/issues/detail?id=12 congenital malformation Albert Goldfain A structurally anomalous part of an organism acquired during fetal development and present at birth (but not necessarily hereditary) which is hypothesized to be harmful for the organism. http://code.google.com/p/ogms/issues/detail?id=28 creation date: 2010-03-31T04:51:11Z treatment creation date: 2010-03-31T04:51:11Z http://code.google.com/p/ogms/issues/detail?id=35 A processual entity whose completion is hypothesized (by a healthcare provider) to alleviate the signs and symptoms associated with a disorder Albert Goldfain convalescence Albert Goldfain http://code.google.com/p/ogms/issues/detail?id=35 creation date: 2010-03-31T04:51:11Z A processual entity during which a patient participating in a disease course gradually returns to participating in a canonical life course. life course creation date: 2010-03-31T04:51:11Z A processual entity which has as parts all the processes in which a given organism is participant. Albert Goldfain http://code.google.com/p/ogms/issues/detail?id=38 prognosis A hypothesis about the course of a disease. creation date: 2010-03-31T12:42:23Z http://code.google.com/p/ogms/issues/detail?id=35 Albert Goldfain acute disease course http://code.google.com/p/ogms/wiki/Meeting_notes_20100513 Albert Goldfain a disease course with a rapid onset but typical unfolding of signs and symptoms after this rapid onset. creation date: 2010-07-19T11:57:44Z inflammation process A process which is a response by an organism's tissues that is generally identified by swelling or localized pain http://code.google.com/p/ogms/wiki/Meeting_notes_20100513 Albert Goldfain creation date: 2010-07-19T11:57:44Z health care process Albert Goldfain creation date: 2011-02-21T09:57:44Z http://groups.google.com/group/ogms-discuss/browse_thread/thread/a2dbc2ed1dff99d6 A social process that has at least one human participant and that includes as parts the treatment, diagnosis, or prevention of disease or injury--or the following of instructions of another human for treatment, diagnosis, or prevention--of a participant in the process health care encounter http://groups.google.com/group/ogms-discuss/browse_thread/thread/a2dbc2ed1dff99d6 A temporally-connected health care process that has as participants an organization or person realizing the health care provider role and a person realizing the patient role. The health care provider role and patient are realized during the health care encounter Albert Goldfain creation date: 2011-02-21T09:57:44Z hospitalization Albert Goldfain creation date: 2011-02-21T09:57:44Z http://groups.google.com/group/ogms-discuss/browse_thread/thread/a2dbc2ed1dff99d6 TODO outpatient encounter TODO http://groups.google.com/group/ogms-discuss/browse_thread/thread/a2dbc2ed1dff99d6 Albert Goldfain creation date: 2011-02-21T09:57:44Z inpatient encounter TODO creation date: 2011-02-21T09:57:44Z Albert Goldfain http://groups.google.com/group/ogms-discuss/browse_thread/thread/a2dbc2ed1dff99d6 ED encounter creation date: 2011-02-21T09:57:44Z http://groups.google.com/group/ogms-discuss/browse_thread/thread/a2dbc2ed1dff99d6 Albert Goldfain TODO injury Albert Goldfain http://groups.google.com/group/ogms-discuss/browse_thread/thread/ca0ad373f27774c5 At the scale of organism (as opposed to the cellular scale or the population scale), an injury is typically the result of a catastrophic event. Consider the implications of making 'injury' a subtype of 'disorder'. A part of an organism that has undergone a change in structural integrity and has a higher chance of dysfunction or causing dysfunction in another structure. creation date: 2011-09-20T09:57:44Z prophylaxis creation date: 2011-09-20T09:57:44Z A planned process that has the objective to reduce the risk of acquiring one or more disorders. Whether or not 'prophylaxis' and 'treatment' classes are disjoint is an open question. http://groups.google.com/group/ogms-discuss/browse_thread/thread/e42bde79218ee34e Albert Goldfain diagnostic process Albert Goldfain http://groups.google.com/group/ogms-discuss/browse_thread/thread/2a7008f311fac766/e7de486c94dfd82e An interpretive process that has as input a clinical picture of a given patient and as output an assertion (diagnostic statement) to the effect that the patient has a disease of such and such a type. creation date: 2011-09-20T09:57:44Z protein An amino acid chain that is produced de novo by ribosome-mediated translation of a genetically-encoded mRNA. PR:000000001 Proteins descended from a common ancestor can be classified into families and superfamilies composed of products of evolutionarily-related genes. The domain architecture of a protein is described by the order of its constituent domains. Proteins with the same domains in the same order are defined as homeomorphic [PRO:WCB]. protein caspase-2 A caspase-1-like protease that is a translation product of the human CASP2 gene or a 1:1 ortholog thereof. This protein is involved in the activation cascade of caspases responsible for apoptosis execution. CASP-2 CASP2 Category=gene. ICH1 NEDD-2 NEDD2 PR:000002311 neural precursor cell expressed developmentally down-regulated protein 2 protease ICH-1 protein Brucella suis 1330 protein A protein that is encoded in the genome of Brucella suis 1330. Bsuis1330 protein PR:000029039 protein Brucella melitensis bv. 1 str. 16M protein A protein that is encoded in the genome of Brucella melitensis bv. 1 str. 16M. Bmel16M protein PR:000029040 protein Brucella abortus bv. 1 str. 9-941 protein A protein that is encoded in the genome of Brucella abortus bv. 1 str. 9-941. Babo9-941 protein PR:000029041 protein Brucella melitensis biovar Abortus 2308 protein A protein that is encoded in the genome of Brucella melitensis biovar Abortus 2308. BmelAbo2308 protein PR:000029044 protein Brucella ovis ATCC 25840 protein A protein that is encoded in the genome of Brucella ovis ATCC 25840. Bovis25840 protein PR:000029049 protein Brucella canis ATCC 23365 protein A protein that is encoded in the genome of Brucella canis ATCC 23365. Bcan23365 protein PR:000029054 protein Brucella melitensis ATCC 23457 protein A protein that is encoded in the genome of Brucella melitensis ATCC 23457. Bmel23457 protein PR:000029058 protein SN-GLYCEROL-3-PHOSPHATE TRANSPORT SYSTEM PERMEASE PROTEIN UGPA Gene name: ugpA NCBIGene: 1198396 This protein is a Brucella virulence factor. MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. NCBIProteinGI: 17988969 PMID: 14638795 UniProtKB: PR:D0B782 LocusTag: BMEII0624 NCBIProteinAccess:NP_541602.1 Molecule Role Annotation: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. nickel ABC transporter, nickel-binding protein, putative LocusTag: BRA0804 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. Gene name: nikA NCBIGene: 1165246 UniProtKB: PR:F8WJW5 NCBIProteinGI: 23500537 NCBIProteinAccess:NP_699977.1 GDP-mannose 4,6-dehydratase Gene name: rfbD LocusTag: BMEI1413 NCBIProteinGI: 17987696 NCBIGene: 1197124 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540330.1 PMID: 14979322 UniProtKB: PR:F8WJX8 phosphoribosylglycinamide formyltransferase LocusTag: BR0709 Molecule Role Annotation: MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. Gene name: purN NCBIProteinAccess:NP_697723.2 NCBIProteinGI: 161486698 NCBIGene: 1166372 PMID: 12761078 This protein is a Brucella virulence factor. MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. UniProtKB: PR:G0K8C8 ferrochelatase NCBIGene: 1197789 NCBIProteinAccess:NP_540995.1 NCBIProteinGI: 17988362 UniProtKB: PR:P0A3D6 LocusTag: BMEII0018 Molecule Role Annotation: FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis Gene name: hemH PMID: last step(Swiss-Prot: P0A3D7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7). SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7). MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. This protein is a Brucella virulence factor. FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis ferrochelatase NCBIProteinGI: 23499843 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis LocusTag: BRA0076 NCBIGene: 1164513 NCBIProteinAccess:NP_699283.1 UniProtKB: PR:P0A3D7 Gene name: hemH PMID: last step(Swiss-Prot: P0A3D7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7). SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7). MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. Molecule Role Annotation: FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis RNA-binding protein Hfq NCBIGene: 1196583 PMID: 14521880, 12730323 NCBIProteinGI: 17987155 This protein is a Brucella virulence factor. FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. Gene name: hfq Molecule Role Annotation: FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. NCBIProteinAccess:NP_539789.1 LocusTag: BMEI0872 UniProtKB: PR:P0A3G7 RNA-binding protein Hfq Gene name: hfq UniProtKB: PR:P0A3G8 Molecule Role Annotation: FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6495:Sonnleitner et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6495:Sonnleitner et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6495:Sonnleitner et al., 2003]. PMID: 14521880 NCBIProteinAccess:NP_698116.1 LocusTag: BR1111 NCBIProteinGI: 23501989 This protein is a Brucella virulence factor. FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6495:Sonnleitner et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6495:Sonnleitner et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6495:Sonnleitner et al., 2003]. NCBIGene: 1166787 OUTER MEMBRANE LIPOPROTEIN PMID: lipid-anchor(Swiss-Prot: P0A3N9). MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9). SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9). MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane NCBIProteinAccess:NP_540994.1 NCBIProteinGI: 17988361 LocusTag: BMEII0017 Gene name: omp10 UniProtKB: PR:P0A3N8 NCBIGene: 1197788 lipoprotein Omp10 NCBIProteinGI: 23499844 Gene name: omp10 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane LocusTag: BRA0077 PMID: lipid-anchor(Swiss-Prot: P0A3N9). MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9). SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9). MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. UniProtKB: PR:P0A3N9 NCBIGene: 1164514 NCBIProteinAccess:NP_699284.1 OUTER MEMBRANE LIPOPROTEIN PMID: lipid-anchor(Swiss-Prot: P0A3P2). MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2). SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2). MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane NCBIProteinGI: 17986419 UniProtKB: PR:P0A3P1 LocusTag: BMEI0135 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane Gene name: omp19 NCBIProteinAccess:NP_539053.1 NCBIGene: 1195847 lipoprotein Omp19 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane NCBIGene: 1167630 NCBIProteinGI: 23502780 This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane LocusTag: BR1930 UniProtKB: PR:P0A3P2 NCBIProteinAccess:NP_698907.1 Gene name: omp19 PMID: lipid-anchor(Swiss-Prot: P0A3P2). MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2). SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2). MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. BP26 This protein is a Brucella virulence factor. MUTATION: A bp26 mutant in Brucella melitensis was attenuated in mice [Ref7374:Cloeckaert et al., 2004]. PMID: 15246618 Gene name: bp26 UniProtKB: PR:P0A3U8 NCBIGene: 1196247 NCBIProteinGI: 1184104 Molecule Role Annotation: MUTATION: A bp26 mutant in Brucella melitensis was attenuated in mice [Ref7374:Cloeckaert et al., 2004]. serine protease NCBIProteinAccess:NP_697625.1 Molecule Role Annotation: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002]. FUNCTION: Protease [Ref412:Kohler et al., 2002]. MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. NCBIProteinGI: 23501498 PMID: 12438693 NCBIGene: 1166273 Gene name: htrA UniProtKB: PR:P0A3Z5 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002]. FUNCTION: Protease [Ref412:Kohler et al., 2002]. MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. LocusTag: BR0611 PHOSPHORIBOSYLAMINOIMIDAZOLE CARBOXYLASE CATALYTIC SUBUNIT Gene name: purE UniProtKB: PR:P52558 NCBIGene: 1196007 NCBIProteinGI: 17986579 Molecule Role Annotation: FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3). CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3). PATHWAY: Nucleotide biosynthesis PMID: IMP biosynthesis LocusTag: BMEI0296 NCBIProteinAccess:NP_539213.1 This protein is a Brucella virulence factor. FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3). CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3). PATHWAY: Nucleotide biosynthesis chorismate synthase LocusTag: BMEI1506 PMID: chorismate biosynthesis NCBIProteinAccess:NP_540423.1 Gene name: aroC Molecule Role Annotation: CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis UniProtKB: PR:P63607 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis NCBIProteinGI: 17987789 NCBIGene: 1197217 chorismate synthase LocusTag: BR0428 PMID: chorismate biosynthesis UniProtKB: PR:P63608 Molecule Role Annotation: CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis NCBIProteinGI: 23501329 NCBIGene: 1166089 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis Gene name: aroC NCBIProteinAccess:NP_697456.1 deoxyuridine 5'-triphosphate nucleotidohydrolase Gene name: dut PMID: 12438693 NCBIProteinAccess:NP_539275.1 This protein is a Brucella virulence factor. FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). NCBIProteinGI: 17986641 NCBIGene: 1196069 LocusTag: BMEI0358 UniProtKB: PR:P64004 Molecule Role Annotation: FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). deoxyuridine 5'-triphosphate nucleotidohydrolase Molecule Role Annotation: FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). LocusTag: BR1675 NCBIProteinGI: 23502533 This protein is a Brucella virulence factor. FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). UniProtKB: PR:P64005 NCBIGene: 1167368 Gene name: dut PMID: 12438693 NCBIProteinAccess:NP_698660.1 GTPase EngB LocusTag: BMEII0274 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: GTPase of unknown function domain, FeoB domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: GTPase of unknown function domain, FeoB domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1198045 Gene name: BMEII0274 UniProtKB: PR:P64066 NCBIProteinGI: 17988618 PMID: 14979322 NCBIProteinAccess:NP_541251.1 ribonucleotide reductase stimulatory protein NCBIProteinAccess:NP_541909 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:P65546 LocusTag: BMEII0931 NCBIProteinGI: 17989276 PMID: 14979322 Gene name: nrdI NCBIGene: 1198703 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, HeLa, but not in Macrophages [Ref6462:Delrue et al., 2004]. GenBank: GG703779 aspartate carbamoyltransferase catalytic subunit NCBIGene: 1198442 PMID: UMP biosynthesis UniProtKB: PR:P65611 NCBIProteinGI: 17989015 NCBIProteinAccess:NP_541648.1 Molecule Role Annotation: CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis Gene name: pyrB LocusTag: BMEII0670 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis aspartate carbamoyltransferase catalytic subunit PMID: UMP biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis NCBIGene: 1165039 NCBIProteinAccess:NP_699783.1 Gene name: pyrB LocusTag: BRA0599 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis UniProtKB: PR:P65612 NCBIProteinGI: 23500343 peptidyl-tRNA hydrolase LocusTag: BMEI0480 PMID: 15385478 This protein is a Brucella virulence factor. FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. NCBIProteinGI: 17986763 NCBIProteinAccess:NP_539397.1 Molecule Role Annotation: FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. Gene name: pth NCBIGene: 1196191 UniProtKB: PR:P65863 peptidyl-tRNA hydrolase Molecule Role Annotation: FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. Gene name: pth This protein is a Brucella virulence factor. FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. NCBIGene: 1167219 UniProtKB: PR:P65864 NCBIProteinGI: 23502404 LocusTag: BR1536 PMID: 15385478 NCBIProteinAccess:NP_698531.1 recombinase A NCBIGene: 1196498 Molecule Role Annotation: FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993]. NCBIProteinGI: 17987070 This protein is a Brucella virulence factor. FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993]. Gene name: recA LocusTag: BMEI0787 NCBIProteinAccess:NP_539704.1 UniProtKB: PR:P65975 PMID: 8321120 recombinase A Gene name: recA NCBIProteinGI: 23502079 NCBIProteinAccess:NP_698206.1 UniProtKB: PR:P65976 PMID: 12414170 Molecule Role Annotation: FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6497:Halling, 2002]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6497:Halling, 2002]. NCBIGene: 1166878 LocusTag: BR1202 This protein is a Brucella virulence factor. FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6497:Halling, 2002]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6497:Halling, 2002]. 50S ribosomal protein L19 Molecule Role Annotation: FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. UniProtKB: PR:P66078 Gene name: rplS This protein is a Brucella virulence factor. FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. NCBIProteinGI: 17986440 LocusTag: BMEI0156 NCBIProteinAccess:NP_539074.1 NCBIGene: 1195868 PMID: 15271960 50S ribosomal protein L19 Gene name: rplS NCBIGene: 1167607 This protein is a Brucella virulence factor. FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. UniProtKB: PR:P66079 Molecule Role Annotation: FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. NCBIProteinGI: 23502758 PMID: 15271960 NCBIProteinAccess:NP_698885.1 LocusTag: BR1907 SUPEROXIDE DISMUTASE (CU-ZN) This protein is a Brucella virulence factor. FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. PMID: 10816475 NCBIGene: 1198353 NCBIProteinAccess:NP_541559.1 UniProtKB: PR:P66826 NCBIProteinGI: 17988926 Molecule Role Annotation: FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. LocusTag: BMEII0581 Gene name: sodC superoxide dismutase, Cu-Zn PMID: 11953393 NCBIGene: 1165145 UniProtKB: PR:P66827 LocusTag: BRA0703 NCBIProteinGI: 23500443 NCBIProteinAccess:NP_699883.1 Gene name: sodC Molecule Role Annotation: FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6481:He et al., 2002][Ref6481:He et al., 2002][Ref6481:He et al., 2002]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6481:He et al., 2002]. This protein is a Brucella virulence factor. FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6481:He et al., 2002][Ref6481:He et al., 2002][Ref6481:He et al., 2002]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6481:He et al., 2002]. bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase Molecule Role Annotation: CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis NCBIProteinGI: 17986517 LocusTag: BMEI0233 NCBIGene: 1195945 UniProtKB: PR:P67539 PMID: IMP biosynthesis NCBIProteinAccess:NP_539151.1 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis Gene name: purH bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase NCBIGene: 1167509 PMID: IMP biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis NCBIProteinAccess:NP_698796.1 NCBIProteinGI: 23502669 UniProtKB: PR:P67540 Gene name: purH LocusTag: BR1816 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis lipoprotein Omp10 Gene name: omp10 NCBIProteinGI: 83269030 UniProtKB: PR:Q2YIP8 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane NCBIProteinAccess:YP_418321.1 This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane PMID: lipid-anchor(Swiss-Prot: P0A3N9). MISCELLANEOUS: Elicits an immune response in B.melitensis-infected sheep but not in B.abortus-infected cattle(Swiss-Prot: P0A3N9). SIMILARITY: Belongs to the rhizobiaceae omp10 lipoprotein family(Swiss-Prot: P0A3N9). MUTATION: Omp10 is an immunoreactive outer membrane lipoprotein. The omp10 mutant was dramatically attenuated for survival in mice and was defective for growth in minimal medium but was not impaired in intracellular growth in vitro, nor does it display clear modification of the outer membrane properties [Ref6473:Tibor et al., 2002]. NCBIGene: 3828036 LocusTag: BAB2_0076 ferrochelatase Molecule Role Annotation: FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis LocusTag: BAB2_0075 Gene name: hemH NCBIProteinAccess:YP_418320.1 NCBIGene: 3828247 NCBIProteinGI: 83269029 PMID: last step(Swiss-Prot: P0A3D7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P0A3D7). SIMILARITY: Belongs to the ferrochelatase family(Swiss-Prot: P0A3D7). MUTATION: A hemH knockout B. abortus mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALBc mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B abortus synthesizes its own heme and also has the ability to use an external source of heme [Ref6472:Almirón et al., 2001]. This protein is a Brucella virulence factor. FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX(Swiss-Prot: P0A3D7). CATALYTIC ACTIVITY: Protoporphyrin + Fe(2+) = protoheme + 2 H(+)(Swiss-Prot: P0A3D7). PATHWAY: Protoheme biosynthesis UniProtKB: PR:Q2YIS9 type IV secretion system protein VirB2 KO: K03197 type IV secretion system protein VirB2 Molecule Role Annotation: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. NCBIProteinAccess:YP_418312.1 LocusTag: BAB2_0067 This protein is a Brucella virulence factor. MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. UniProtKB: PR:Q2YIT6 NCBIGene: 3827981 NCBIProteinGI: 83269021 Gene name: virB2 PMID: 15322008, 16113325 Type IV secretory pathway, VirB3-like This protein is a Brucella virulence factor. MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. NCBIProteinAccess:YP_418311.1 Gene name: virB3 Molecule Role Annotation: MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. UniProtKB: PR:Q2YIT7 NCBIProteinGI: 83269020 LocusTag: BAB2_0066 NCBIGene: 3827980 PMID: 12761078 attachment mediating protein virB5 homolog KO: K03200 type IV secretion system protein VirB5 NCBIProteinAccess:YP_418309.1 NCBIGene: 3827978 This protein is a Brucella virulence factor. MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. Molecule Role Annotation: MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. Gene name: virB5 PMID: 12595417, 12595466, 16113325, 10510235 LocusTag: BAB2_0064 UniProtKB: PR:Q2YJ75 NCBIProteinGI: 83269018 VirB8 PMID: 10678941, 12414149 Molecule Role Annotation: MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. UniProtKB: PR:Q2YJ78 NCBIGene: 3827898 NCBIProteinGI: 83269015 NCBIProteinAccess:YP_418306.1 LocusTag: BAB2_0061 Gene name: virB8 This protein is a Brucella virulence factor. MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. glutamate synthase subunit beta NCBIGene: 3828240 This protein is a Brucella virulence factor. MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. PMID: 10858227 NCBIProteinAccess:YP_418299.1 Molecule Role Annotation: MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. NCBIProteinGI: 83269008 Gene name: gltD UniProtKB: PR:Q2YJ86 LocusTag: BAB2_0054 6-phosphogluconate dehydrogenase NCBIProteinAccess:YP_418351.1 Molecule Role Annotation: MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. UniProtKB: PR:Q2YJ89 LocusTag: BAB2_0109 This protein is a Brucella virulence factor. MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. Gene name: gnd PMID: 12761078 NCBIGene: 3828241 NCBIProteinGI: 83269060 flagellar MS-ring protein NCBIGene: 3828220 NCBIProteinAccess:YP_419232.1 PMID: multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3). SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3). MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. LocusTag: BAB2_1105 Molecule Role Annotation: FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane NCBIProteinGI: 83269941 This protein is a Brucella virulence factor. FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane UniProtKB: PR:Q2YJF2 Gene name: fliF flagellar motor protein MotB UniProtKB: PR:Q2YJF4 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 3827414 PMID: 14979322 NCBIProteinGI: 83269939 NCBIProteinAccess:YP_419230.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BAB2_1103 Gene name: motB flagellar hook protein FlgE NCBIGene: 3827409 Gene name: flgE PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:YP_419225.1 NCBIProteinGI: 83269934 LocusTag: BAB2_1098 UniProtKB: PR:Q2YJF9 ATP/GTP-binding site motif A (P-loop):ABC transporter:AAA ATPase NCBIProteinGI: 83269919 NCBIProteinAccess:YP_419210.1 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: znuC UniProtKB: PR:Q2YJH4 NCBIGene: 3827702 LocusTag: BAB2_1080 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Periplasmic solute binding protein NCBIProteinAccess:YP_419209.1 LocusTag: BAB2_1079 NCBIProteinGI: 83269918 Molecule Role Annotation: MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. NCBIGene: 3827700 PMID: 12761078 This protein is a Brucella virulence factor. MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. Gene name: znuA UniProtKB: PR:Q2YJH5 Nitrate reductase, alpha subunit:Prokaryotic molybdopterin oxidoreductase:Molybdopterin oxidoreductase:Molydopterin dinucleot... UniProtKB: PR:Q2YJY4 NCBIProteinGI: 83269759 NCBIProteinAccess:YP_419050.1 NCBIGene: 3827924 Gene name: narG PMID: 12438693 LocusTag: BAB2_0904 Molecule Role Annotation: MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. This protein is a Brucella virulence factor. MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Glutaredoxin Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. LocusTag: BAB2_0891 PMID: 14979322 NCBIProteinAccess:YP_419043.1 Gene name: nrdH This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 83269752 UniProtKB: PR:Q2YJZ1 NCBIGene: 3827703 Beta and gamma crystallin:Cytochrome bd ubiquinol oxidase, subunit II PMID: 11274104 UniProtKB: PR:Q2YKD5 NCBIGene: 3828142 Gene name: cydB Molecule Role Annotation: MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. NCBIProteinAccess:YP_418899.1 This protein is a Brucella virulence factor. MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. NCBIProteinGI: 83269608 LocusTag: BAB2_0727 aspartate carbamoyltransferase catalytic subunit UniProtKB: PR:Q2YKL8 NCBIProteinAccess:YP_418816.1 NCBIGene: 3827823 PMID: UMP biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis NCBIProteinGI: 83269525 Gene name: pyrB This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate(Swiss-Prot: P65612). PATHWAY: Nucleotide biosynthesis LocusTag: BAB2_0641 Response regulator receiver This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 3828149 NCBIProteinGI: 83269512 Gene name: divK Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. LocusTag: BAB2_0628 NCBIProteinAccess:YP_418803.1 PMID: 14979322 UniProtKB: PR:Q2YKN1 Bacterial extracellular solute-binding protein, family 1 PMID: 16817909 NCBIProteinGI: 83269478 NCBIGene: 3827694 Gene name: ugpB LocusTag: BAB2_0585 This protein is a Brucella virulence factor. MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. NCBIProteinAccess:YP_418769.1 UniProtKB: PR:Q2YKR5 Molecule Role Annotation: MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. Binding-protein-dependent transport systems inner membrane component:Blood group Rhesus C/E and D polypeptide NCBIProteinGI: 83269477 Gene name: ugpA PMID: 14638795 This protein is a Brucella virulence factor. MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. NCBIGene: 3827693 UniProtKB: PR:Q2YKR6 LocusTag: BAB2_0584 Molecule Role Annotation: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. NCBIProteinAccess:YP_418768.1 Copper/Zinc superoxide dismutase UniProtKB: PR:Q2YKV9 Gene name: sodC Molecule Role Annotation: FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. PMID: 10816475 NCBIProteinGI: 83269434 NCBIGene: 3827840 LocusTag: BAB2_0535 NCBIProteinAccess:YP_418725.1 This protein is a Brucella virulence factor. FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity)(Swiss-Prot: P66827). CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2)(Swiss-Prot: P66827). COFACTOR: Binds 1 copper ion per subunit (By similarity)(Swiss-Prot: P66827). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: P66827). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: P66827). SUBCELLULAR LOCATION: Periplasmic (By similarity)(Swiss-Prot: P66827). SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family(Swiss-Prot: P66827). IMMUNOGENICITY: Induces antigen-specific Th1 immune response, as indicated by the specific induction of serum IgG2a, but not IgG1, antibodies and by the secretion of IFN-?, but not IL-4, by the Cu/Zn SOD-stimulated splenocytes. Has been used for vaccine development [Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000][Ref6552:Vemulapalli et al., 2000]. MUTATION: An isogenic sodC mutant constructed from B abortus 2308 by gene replacement exhibited much greater susceptibility to killing by exogenous O(2)(-) than the parental 2308 strain, supporting a role for SodC in protecting this bacterium from O(2)(-) stress. The B abortus sodC mutant was much more sensitive to killing by cultured resident peritoneal macrophages from C57BL6J mice than 2308, and its attenuation in cultured murine macrophages was enhanced when these phagocytes were treated with gamma interferon. The attenuation of the B abortus sodC mutant in both resting and IFN-gamma -activated macrophages was alleviated in the presence of the NADPH oxidase inhibitor apocynin. Consistently, the B abortus sodC mutant also displayed significant attenuation in infected C57BL6J mice compared to the parental strain. These findings suggest that SodC protects B abortus 2308 from the respiratory burst of host macrophages [Ref6552:Vemulapalli et al., 2000]. glycine dehydrogenase This protein is a Brucella virulence factor. FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor Gene name: gcvP PMID: CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-Prot: Q8FVU9). CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-Prot: Q8FVU9). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FVU9). SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-Prot: Q8FVU9). SIMILARITY: Belongs to the gcvP family(Swiss-Prot: Q8FVU9). MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ref6482:Ficht, 2003]. NCBIProteinAccess:YP_418705.1 Molecule Role Annotation: FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor NCBIGene: 3828233 UniProtKB: PR:Q2YKX9 NCBIProteinGI: 83269414 LocusTag: BAB2_0515 Glycine cleavage T protein (aminomethyl transferase) UniProtKB: PR:Q2YKY1 Gene name: gcvT NCBIProteinGI: 83269412 NCBIGene: 3828234 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinAccess:YP_418703.1 PMID: 12438693 LocusTag: BAB2_0513 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. exodeoxyribonuclease VII large subunit PMID: 14638795 Gene name: xseA NCBIGene: 3827916 UniProtKB: PR:Q2YL15 This protein is a Brucella virulence factor. FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. Molecule Role Annotation: FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. NCBIProteinAccess:YP_418669.1 NCBIProteinGI: 83269378 LocusTag: BAB2_0475 pyruvate carboxylase NCBIProteinGI: 82700564 This protein is a Brucella virulence factor. MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. Molecule Role Annotation: MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. LocusTag: BAB1_1791 NCBIProteinAccess:YP_415138.1 NCBIGene: 3788880 PMID: 10678941 Gene name: pyc UniProtKB: PR:Q2YLG1 bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase UniProtKB: PR:Q2YLH0 NCBIProteinAccess:YP_415170.1 LocusTag: BAB1_1824 Gene name: purH This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). CATALYTIC ACTIVITY: IMP + H(2)O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide(Swiss-Prot: P67540). PATHWAY: Nucleotide biosynthesis NCBIProteinGI: 82700596 NCBIGene: 3788876 PMID: IMP biosynthesis 50S ribosomal protein L19 NCBIProteinAccess:YP_415248.1 NCBIGene: 3788922 NCBIProteinGI: 82700674 UniProtKB: PR:Q2YLP6 PMID: 15271960 Molecule Role Annotation: FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. Gene name: rplS This protein is a Brucella virulence factor. FUNCTION: This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity)(Swiss-Prot: P66079). SIMILARITY: Belongs to the ribosomal protein L19P family(Swiss-Prot: P66079). MUTATION: rplS is involved in traanslation. B. abortus rplS mutant by the mini-Tn5 disruption displays nutritional defects in vitro [Ref6485:Alcantara et al., 2004]. LocusTag: BAB1_1906 isopropylmalate isomerase large subunit Molecule Role Annotation: FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis PMID: L-leucine biosynthesis NCBIProteinGI: 82700673 LocusTag: BAB1_1905 NCBIProteinAccess:YP_415247.1 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis NCBIGene: 3788772 UniProtKB: PR:Q2YLP7 Gene name: leuC lipoprotein Omp19 PMID: lipid-anchor(Swiss-Prot: P0A3P2). MISCELLANEOUS: Elicits an immune response in humans, mice, sheep and goats infected with B.melitensis or B.abortus, but not in B.abortus-infected cattle(Swiss-Prot: P0A3P2). SIMILARITY: Belongs to the rhizobiaceae omp19 lipoprotein family(Swiss-Prot: P0A3P2). MUTATION: Omp19 is an immunoreactive outer membrane lipoprotein. Significantly fewer brucellae were recovered from the spleens of mice infected with the omp19 mutant than from those of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19 mutant exhibited an increase in sensitivity to the polycation polymyxin B and to sodium deoxycholate. These results indicate that inactivation of the omp19 gene alters the outer membrane properties of B abortus [Ref6473:Tibor et al., 2002]. UniProtKB: PR:Q2YLR6 NCBIGene: 3788831 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane NCBIProteinGI: 82700695 Gene name: omp19 NCBIProteinAccess:YP_415269.1 LocusTag: BAB1_1930 peptidyl-tRNA hydrolase NCBIProteinAccess:YP_414918.1 NCBIGene: 3788869 NCBIProteinGI: 82700344 Gene name: pth LocusTag: BAB1_1552 UniProtKB: PR:Q2YLX5 Molecule Role Annotation: FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. This protein is a Brucella virulence factor. FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity)(Swiss-Prot: P65864). CATALYTIC ACTIVITY: N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA(Swiss-Prot: P65864). SUBUNIT: Monomer (By similarity)(Swiss-Prot: P65864). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65864). SIMILARITY: Belongs to the PTH family(Swiss-Prot: P65864). MUTATION: pth encodes for a peptidyl tRNA hydrolase. Transposon insertion in pth has a polar effect on dugA expression and that the pth/dugA mutant is deficient in iron assimilation because of altered expression of the dugA gene. Only minor difference in intracellular growth in bovine macrophages and HeLa cells between the pth/dugA mutant and wild-type strains was observed [Ref6498:Danese et al., 2004]. PMID: 15385478 Glyoxalase/Bleomycin resistance protein/dioxygenase domain:Glyoxalase I NCBIGene: 3788728 NCBIProteinGI: 82700098 PMID: 14979322 NCBIProteinAccess:YP_414672.1 Gene name: gloA UniProtKB: PR:Q2YM78 LocusTag: BAB1_1286 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. transport protein PMID: 10741969 This protein is a Brucella virulence factor. MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. UniProtKB: PR:Q2YMA1 Gene name: bacA NCBIGene: 3788635 Molecule Role Annotation: MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. NCBIProteinGI: 82699288 NCBIProteinAccess:YP_413862.1 LocusTag: BAB1_0402 phosphoribosylamine--glycine ligase NCBIGene: 3788874 LocusTag: BAB1_0442 PMID: IMP biosynthesis UniProtKB: PR:Q2YMD3 NCBIProteinGI: 82699328 Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis Gene name: purD This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis NCBIProteinAccess:YP_413902.1 chorismate synthase NCBIProteinGI: 82699340 Molecule Role Annotation: CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis PMID: chorismate biosynthesis This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate + phosphate(Swiss-Prot: P63608). COFACTOR: Reduced flavin (By similarity)(Swiss-Prot: P63608). PATHWAY: Metabolic intermediate biosynthesis LocusTag: BAB1_0454 UniProtKB: PR:Q2YMF8 Gene name: aroC NCBIProteinAccess:YP_413914.1 NCBIGene: 3788622 amidophosphoribosyltransferase NCBIProteinGI: 82699358 NCBIGene: 3788875 This protein is a Brucella virulence factor. MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. NCBIProteinAccess:YP_413932.1 Molecule Role Annotation: MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. PMID: 12761078 UniProtKB: PR:Q2YMH7 Gene name: purF LocusTag: BAB1_0472 Short-chain dehydrogenase/reductase SDR:GDP-mannose 4,6-dehydratase NCBIGene: 3788735 LocusTag: BAB1_0545 PMID: 15099501 Molecule Role Annotation: MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. Gene name: gmd UniProtKB: PR:Q2YMP3 NCBIProteinGI: 82699425 This protein is a Brucella virulence factor. MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. NCBIProteinAccess:YP_413999.1 ABC transporter, family 2:Acriflavin resistance protein Gene name: rfbD NCBIProteinGI: 82699423 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:YP_413997.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BAB1_0543 NCBIGene: 3788901 PMID: 14979322 UniProtKB: PR:Q2YMP5 Membrane alanine aminopeptidase:Neutral zinc metallopeptidase, zinc-binding region This protein is a Brucella virulence factor. MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. NCBIProteinAccess:YP_414083.1 UniProtKB: PR:Q2YMX0 Gene name: pepN Molecule Role Annotation: MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. NCBIProteinGI: 82699509 PMID: 12933870 NCBIGene: 3788843 LocusTag: BAB1_0641 phosphoribosylaminoimidazole synthetase Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis PMID: IMP biosynthesis NCBIProteinGI: 82699599 NCBIProteinAccess:YP_414173.1 LocusTag: BAB1_0731 NCBIGene: 3788878 UniProtKB: PR:Q2YN59 Gene name: purM phosphoribosylglycinamide formyltransferase PMID: 12761078 UniProtKB: PR:Q2YN60 Molecule Role Annotation: MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. NCBIProteinGI: 162002876 Gene name: purN LocusTag: BAB1_0730 NCBIGene: 3788879 NCBIProteinAccess:YP_414172.2 This protein is a Brucella virulence factor. MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. serine hydroxymethyltransferase UniProtKB: PR:Q2YN95 PMID: 12438693 NCBIProteinGI: 82699646 NCBIProteinAccess:YP_414220.1 Molecule Role Annotation: FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: glyA This protein is a Brucella virulence factor. FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 3788734 LocusTag: BAB1_0787 trigger factor PMID: 14638795 NCBIProteinGI: 82699768 NCBIGene: 3787589 Molecule Role Annotation: FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. LocusTag: BAB1_0917 This protein is a Brucella virulence factor. FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. Gene name: tig UniProtKB: PR:Q2YNL3 NCBIProteinAccess:YP_414342.1 dihydroxy-acid dehydratase Molecule Role Annotation: CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis Gene name: ilvD NCBIProteinAccess:YP_413592.1 LocusTag: BAB1_0096 UniProtKB: PR:Q2YNW9 PMID: L-isoleucine biosynthesis NCBIProteinGI: 82699018 NCBIGene: 3788763 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis Nitrite/sulfite reductase ferredoxin-like half domain:Nitrite and sulfite reductase iron-sulfur/siroheme-binding site:Nitrite... LocusTag: BAB1_0181 UniProtKB: PR:Q2YP26 NCBIProteinGI: 82699095 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: cysI NCBIGene: 3788677 NCBIProteinAccess:YP_413669.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. B12-dependent methionine synthase This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:YP_413676.1 UniProtKB: PR:Q2YP51 NCBIProteinGI: 82699102 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: metH NCBIGene: 3786978 LocusTag: BAB1_0188 histidinol dehydrogenase Gene name: hisD NCBIProteinGI: 82699185 UniProtKB: PR:Q2YPB8 NCBIProteinAccess:YP_413759.1 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis NCBIGene: 3788752 PMID: L-histidine biosynthesis Molecule Role Annotation: FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis LocusTag: BAB1_0285 glucose-6-phosphate isomerase Gene name: pgi UniProtKB: PR:Q2YPF3 NCBIProteinAccess:YP_413784.1 NCBIProteinGI: 82699210 Molecule Role Annotation: CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation PMID: glycolysis This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation NCBIGene: 3787092 LocusTag: BAB1_0316 dihydroorotate dehydrogenase 2 UniProtKB: PR:Q2YPG3 NCBIProteinGI: 82699235 NCBIGene: 3788883 PMID: 12761078 NCBIProteinAccess:YP_413809.1 Molecule Role Annotation: MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. This protein is a Brucella virulence factor. MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. Gene name: pyrD LocusTag: BAB1_0341 prephenate dehydratase PMID: 15271960 NCBIGene: 3788850 NCBIProteinGI: 82698963 Gene name: pheA This protein is a Brucella virulence factor. MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. NCBIProteinAccess:YP_413537.1 LocusTag: BAB1_0034 Molecule Role Annotation: MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. UniProtKB: PR:Q2YPM5 30S ribosomal protein S1 NCBIProteinAccess:YP_413528.1 LocusTag: BAB1_0025 Molecule Role Annotation: MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. UniProtKB: PR:Q2YPN4 This protein is a Brucella virulence factor. MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. NCBIGene: 3788939 Gene name: rpsA NCBIProteinGI: 82698954 PMID: 10678941 phosphoglucomutase Gene name: pgm PMID: 10992476 Molecule Role Annotation: MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. NCBIProteinAccess:YP_413555.1 UniProtKB: PR:Q2YPS4 NCBIProteinGI: 82698981 LocusTag: BAB1_0055 NCBIGene: 3788847 This protein is a Brucella virulence factor. MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. CbxX/CfqX superfamily:Response regulator receiver:Sigma-54 factor interaction domain:Helix-turn-helix, Fis-type:AAA ATPase Gene name: ntrC Molecule Role Annotation: MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. This protein is a Brucella virulence factor. MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. NCBIProteinGI: 82699958 NCBIProteinAccess:YP_414532.1 NCBIGene: 3788817 UniProtKB: PR:Q2YPW4 LocusTag: BAB1_1140 PMID: 10373105 PAS domain:ATP-binding region, ATPase-like:Histidine kinase, HAMP region:Histidine kinase A, N-terminal:Bacterial sensor prot... PMID: 10678941 UniProtKB: PR:Q2YPW5 NCBIProteinGI: 82699957 NCBIProteinAccess:YP_414531.1 This protein is a Brucella virulence factor. MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. Gene name: ntrY NCBIGene: 3788818 LocusTag: BAB1_1139 Molecule Role Annotation: MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. RNA-binding protein Hfq NCBIProteinGI: 82699953 Molecule Role Annotation: FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. PMID: 14521880, 12730323 Gene name: hfq NCBIGene: 3788748 NCBIProteinAccess:YP_414527.1 This protein is a Brucella virulence factor. FUNCTION: RNA-binding protein that stimulates the elongation of poly(A) tails (By similarity)(Swiss-Prot: P0A3G8). SIMILARITY: Belongs to the hfq family(Swiss-Prot: P0A3G8). MUTATION: hfq encodes for the RNA binding protein host factor I (HF-I). The hfq knock out strain has been showed a reduced growth rate and is unable to utilize glucose as a sole carbon source[Ref6495:Sonnleitner et al., 2003]. hfq is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B melitensis counterpart in experimentally infected animals indicate that stationary -phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages [Ref6532:Roop et al., 2003]. In contrast to B abortus 2308, the isogenic hfq and bacA mutants remained in acidic, LAMP-1 phagosomes and failed to initiate intracellular replication [Ref6532:Roop et al., 2003]. A hfq mutant of B abortus was eliminated from mouse spleens more rapidly than the wild type [Ref6532:Roop et al., 2003]. UniProtKB: PR:Q2YPW9 LocusTag: BAB1_1134 excinuclease ABC subunit A Gene name: uvrA Molecule Role Annotation: FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. PMID: 16816190 NCBIProteinGI: 82699947 NCBIProteinAccess:YP_414521.1 LocusTag: BAB1_1128 NCBIGene: 3787776 UniProtKB: PR:Q2YPX5 This protein is a Brucella virulence factor. FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. Glutamine synthetase class-I, adenylation site:Glutamine synthetase type I:Glutamine synthetase, catalytic domain:Glutamine s... Gene name: glnA NCBIProteinAccess:YP_414429.1 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 3788725 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinGI: 82699855 PMID: 12438693 UniProtKB: PR:Q2YQ67 LocusTag: BAB1_1023 tRNA-Lys NCBIGene: 3787926 NCBIProteinGI: 2353000 UniProtKB: PR:Q2YQE8 Gene name: asp24 Molecule Role Annotation: MUTATION: A asp24 mutation in Brucella abortus is attenuated in mice [Ref7373:Kahl-McDonagh et al., 2007]. This protein is a Brucella virulence factor. MUTATION: A asp24 mutation in Brucella abortus is attenuated in mice [Ref7373:Kahl-McDonagh et al., 2007]. PMID: 17664263 NCBIProteinAccess:AAB69346.1 imidazole glycerol phosphate synthase subunit HisF Molecule Role Annotation: FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis Gene name: hisF This protein is a Brucella virulence factor. FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 82700840 LocusTag: BAB1_2086 UniProtKB: PR:Q2YQY8 NCBIGene: 3788754 NCBIProteinAccess:YP_415414.1 PMID: L-histidine biosynthesis histidinol-phosphate aminotransferase This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98). PATHWAY: Amino-acid biosynthesis UniProtKB: PR:Q2YR81 NCBIProteinAccess:YP_415321.1 NCBIGene: 3788751 PMID: L-histidine biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98). PATHWAY: Amino-acid biosynthesis LocusTag: BAB1_1988 Gene name: hisC NCBIProteinGI: 82700747 Phosphoribosyltransferase:Hypoxanthine phosphoribosyl transferase NCBIProteinAccess:YP_415319.1 UniProtKB: PR:Q2YR83 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BAB1_1986 NCBIProteinGI: 82700745 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: hpt NCBIGene: 3788755 Orn/DAP/Arg decarboxylase, family 2:ATP/GTP-binding site motif A (P-loop):Diaminopimelate decarboxylase This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 3788788 UniProtKB: PR:Q2YR85 NCBIProteinAccess:YP_415317.1 PMID: 12438693 Gene name: lysA Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. LocusTag: BAB1_1984 NCBIProteinGI: 82700743 phosphoglycerate kinase PMID: 20194591 LocusTag: BAB1_1742 GenBank: AM040264 NCBIProteinAccess:YP_415092 NCBIProteinGI: 82700518 UniProtKB: PR:Q2YRD9 Molecule Role Annotation: MUTATION: A pgk mutant is attenuated in mice [Ref7376:Trant et al., 2010]. This protein is a Brucella virulence factor. MUTATION: A pgk mutant is attenuated in mice [Ref7376:Trant et al., 2010]. Gene name: pgk NCBIGene: 3788256 deoxyuridine 5'-triphosphate nucleotidohydrolase This protein is a Brucella virulence factor. FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). NCBIProteinAccess:YP_415037.1 PMID: 12438693 UniProtKB: PR:Q2YRG4 NCBIGene: 3788687 LocusTag: BAB1_1687 Gene name: dut NCBIProteinGI: 82700463 Molecule Role Annotation: FUNCTION: This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA (By similarity)(Swiss-Prot: P64005). CATALYTIC ACTIVITY: dUTP + H(2)O = dUMP + diphosphate(Swiss-Prot: P64005). PATHWAY: De novo synthesis of thymidylate(Swiss-Prot: P64005). SIMILARITY: Belongs toMUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis dut gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. the dUTPase family(Swiss-Prot: P64005). aspartate aminotransferase NCBIProteinGI: 82700306 This protein is a Brucella virulence factor. MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. NCBIGene: 3788626 LocusTag: BAB1_1514 UniProtKB: PR:Q2YRM6 Gene name: aspC Molecule Role Annotation: MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. PMID: 12761078 NCBIProteinAccess:YP_414880.1 2-isopropylmalate synthase UniProtKB: PR:Q2YRT1 LocusTag: BAB1_1583 NCBIProteinAccess:YP_414947.2 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis PMID: L-leucine biosynthesis Molecule Role Annotation: FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis Gene name: leuA NCBIProteinGI: 162002872 NCBIGene: 3788771 DNA-directed RNA polymerase subunit alpha Molecule Role Annotation: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. NCBIGene: 3788935 Gene name: rpoA NCBIProteinGI: 82700043 PMID: 14638795 UniProtKB: PR:Q2YRU0 LocusTag: BAB1_1231 NCBIProteinAccess:YP_414617.1 This protein is a Brucella virulence factor. FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. recombinase A This protein is a Brucella virulence factor. FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993]. UniProtKB: PR:Q2YRU7 LocusTag: BAB1_1224 NCBIProteinAccess:YP_414610.1 NCBIProteinGI: 82700036 Molecule Role Annotation: FUNCTION: Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with lexA causing its activation and leading to its autocatalytic cleavage (By similarity)(Swiss-Prot: P65976). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: P65976). SIMILARITY: Belongs to the recA family(Swiss-Prot: P65976). MUTATION: The RecA mutant was more sensitive than the parental strain to killing by MMS. When administered intraperitoneally to BALBc mice, numbers of bacteria per spleen were consistently lower in animals infected with the RecA mutant than with the parental strain. However, both the RecA mutant and parental strain persisted in mice through 100 days post-infection. These results indicate that RecA is not crucial for persistence of B abortus in mice [Ref6531:Tatum et al., 1993]. The B abortus RecA mutant was virulent in mice, but its course of infection in mice differed from that of the parental strain. The infectious cycle of the parental strain in the mouse model was biphasic. During the rst week, there was an initial rise in cfu of B abortus 2308 in the spleen followed by a decrease during the second week. This phase was followed by a second phase in which B abortus S2308 persisted and slowly increased in numbers in the spleen . Though fewer RecA mutants were found in the spleens of mice infected intraperitoneally in the early stages of the infection and no large initial rise was seen, the same numbers were found as the parental strain 100 days post -infection. This suggests that collectively, different loci are involved to varying extents in the initial infection and the persistence phase [Ref6531:Tatum et al., 1993]. Gene name: recA PMID: 8321120 NCBIGene: 3788897 tRNA delta(2)-isopentenylpyrophosphate transferase LocusTag: BAB1_1409 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 3787973 NCBIProteinAccess:YP_414781.1 Molecule Role Annotation: FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: miaA PMID: 12438693 NCBIProteinGI: 82700207 UniProtKB: PR:Q2YS31 25 KDA OUTER-MEMBRANE IMMUNOGENIC PROTEIN PRECURSOR NCBIGene: 1196960 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689). SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689). MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. NCBIProteinGI: 17987532 UniProtKB: PR:Q45321 NCBIProteinAccess:NP_540166.1 LocusTag: BMEI1249 This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689). SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689). MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. Gene name: omp25 PMID: 11447156 outer-membrane protein Omp25 NCBIProteinGI: 23501588 Molecule Role Annotation: SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689). SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689). MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. NCBIGene: 1166364 LocusTag: BR0701 NCBIProteinAccess:NP_697715.1 Gene name: omp25 UniProtKB: PR:Q45689 PMID: 11447156 This protein is a Brucella virulence factor. SUBCELLULAR LOCATION: Outer membrane(Swiss-Prot: Q45689). SIMILARITY: Belongs to the omp25/ropB family(Swiss-Prot: Q45689). MUTATION: In contrast to WT B suis or Deltaomp31 B suis, Deltaomp25 B suis induced TNF-alpha production when phagocytosed by human macrophages. So Omp25 of B suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages [Ref6492:Jubier-Maurin et al., 2001]. To determine the role of Omp25 in virulence, mutants were created with Brucella abortus (BA25), Brucella melitensis (BM25), and Brucella ovis (BO25) which contain disruptions in the omp25 gene (Deltaomp25 mutants). BALBc mice infected with B abortus BA25 or B melitensis BM25 showed a significant decrease in mean CFUspleen at 18 and 4 weeks post-infection, respectively, when compared to the virulent parental strain. Mice infected with B ovis BO25 had significantly lower mean CFUspleen counts from 1 to 8 weeks post-infection, at which point the mutant was cleared from the spleens. Murine vaccination with either BM25 or the current caprine vaccine B melitensis strain Rev.1 resulted in more than a 2log (10) reduction in bacterial load following challenge with virulent B melitensis. Vaccination of mice with the B ovis mutant resulted in clearance of the challenge strain and provided 2.5log (10) greater protection against virulent B ovis than vaccine strain Rev.1. Based on these data, the B melitensis and B ovis Deltaomp25 mutants are interesting vaccine candidates that are currently under study in our laboratory for their safety and efficacy in small ruminants [Ref6492:Jubier-Maurin et al., 2001]. Although they are slightly attenuated, B abortus omp25 and omp22 mutants do not show the high level of attenuation and sensitivity to bactericidal peptides displayed by the bvrS and bvrR mutants [Ref6492:Jubier-Maurin et al., 2001]. B abortus mutants carrying Omp25 deletions do not show enrichment of underacylated LPS [Ref6492:Jubier-Maurin et al., 2001]. Brucella spp. omp25 deletion mutants are attenuated in mice, cattle and goats, showing the involvement of Brucella spp. Omp25 in virulence [Ref6492:Jubier-Maurin et al., 2001]. type IV secretion system protein VirB2 NCBIProteinAccess:NP_699275.1 Molecule Role Annotation: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6470:Sun et al., 2005]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. PMID: 16113325 UniProtKB: PR:Q7CEG0 This protein is a Brucella virulence factor. MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6470:Sun et al., 2005]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. Gene name: virB2 NCBIGene: 1164505 NCBIProteinGI: 23499835 LocusTag: BRA0068 type IV secretion system protein VirB3 Molecule Role Annotation: MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. UniProtKB: PR:Q7CEG1 LocusTag: BRA0067 Gene name: virB3 NCBIProteinAccess:NP_699274.1 NCBIGene: 1164504 NCBIProteinGI: 23499834 PMID: 12761078 This protein is a Brucella virulence factor. MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. type IV secretion system protein VirB8 Gene name: virB8 Molecule Role Annotation: MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. PMID: 12414149 This protein is a Brucella virulence factor. MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. NCBIProteinGI: 23499829 LocusTag: BRA0062 UniProtKB: PR:Q7CEG3 NCBIProteinAccess:NP_699269.1 NCBIGene: 1164499 TRANSCRIPTIONAL REGULATORY PROTEIN PHOP LocusTag: BMEI1337 NCBIProteinAccess:NP_540254.1 Gene name: feuP NCBIGene: 1197048 NCBIProteinGI: 17987620 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q7CNU2 tRNA delta(2)-isopentenylpyrophosphate transferase NCBIProteinGI: 23502261 LocusTag: BR1390 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB: PR:Q8CY40 NCBIGene: 1167072 NCBIProteinAccess:NP_698388.1 Molecule Role Annotation: FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: miaA PMID: 12438693 RelA/SpoT family protein NCBIProteinGI: 23501539 LocusTag: BR0652 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_697666.1 Gene name: spotT NCBIGene: 1166315 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8CY42 flagellar MS-ring protein NCBIGene: 1165599 This protein is a Brucella virulence factor. FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane Gene name: fliF LocusTag: BRA1146 Molecule Role Annotation: FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane NCBIProteinGI: 23500860 NCBIProteinAccess:NP_700300.1 UniProtKB: PR:Q8FUS3 PMID: multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3). SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3). MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. flagellar motor protein MotB Gene name: motB Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23500858 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1165597 NCBIProteinAccess:NP_700298.1 LocusTag: BRA1144 UniProtKB: PR:Q8FUS5 flagellar hook protein FlgE UniProtKB: PR:Q8FUS9 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23500854 NCBIGene: 1165592 Gene name: flgE NCBIProteinAccess:NP_700294.1 LocusTag: BRA1139 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. zinc ABC transporter, ATP-binding protein NCBIProteinAccess:NP_700278.1 LocusTag: BRA1123 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: znuC UniProtKB: PR:Q8FUU5 PMID: 14979322 NCBIProteinGI: 23500838 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1165576 zinc ABC transporter, periplasmic zinc-binding protein UniProtKB: PR:Q8FUU6 NCBIProteinAccess:NP_700277.1 Molecule Role Annotation: MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. LocusTag: BRA1122 NCBIProteinGI: 23500837 NCBIGene: 1165575 This protein is a Brucella virulence factor. MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6469:Kim et al., 2003]. Gene name: znuA PMID: 12761078 ABC transporter, periplasmic substrate-binding protein NCBIProteinGI: 23500735 NCBIProteinAccess:NP_700175.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BRA1012 UniProtKB: PR:Q8FV39 PMID: 14979322 NCBIGene: 1165456 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: dppA (not ortho to BRUME) cobalamin synthesis protein/P47K family protein NCBIProteinAccess:NP_700151.1 NCBIProteinGI: 23500711 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: cobW PMID: 12438693 NCBIGene: 1165431 LocusTag: BRA0987 UniProtKB: PR:Q8FV62 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. D-aminopeptidase LocusTag: BRA0947 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23500673 UniProtKB: PR:Q8FV99 PMID: 14979322 NCBIGene: 1165391 Gene name: dacF This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_700113.1 sugar ABC transporter, ATP-binding protein PMID: 14979322 UniProtKB: PR:Q8FVA9 Gene name: araG This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_700103.1 NCBIProteinGI: 23500663 NCBIGene: 1165380 LocusTag: BRA0936 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. oxidoreductase, molybdopterin-binding, putative Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FVC5 LocusTag: BRA0919 PMID: 14979322 NCBIGene: 1165363 NCBIProteinGI: 23500646 NCBIProteinAccess:NP_700086.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. Gene name: fdhA D-erythrulose-1-phosphate dehydrogenase This protein is a Brucella virulence factor. MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6483:Sangari et al., 2000]. PMID: 10708387 UniProtKB: PR:Q8FVH5 NCBIGene: 1165309 NCBIProteinGI: 23500594 NCBIProteinAccess:NP_700034.1 Gene name: eryC LocusTag: BRA0866 Molecule Role Annotation: MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6483:Sangari et al., 2000]. glycerol-3-phosphate dehydrogenase PMID: 10708387 LocusTag: BRA0865 Molecule Role Annotation: MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6483:Sangari et al., 2000]. NCBIGene: 1165308 UniProtKB: PR:Q8FVH6 Gene name: eryB NCBIProteinGI: 23500593 NCBIProteinAccess:NP_700033.1 This protein is a Brucella virulence factor. MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6483:Sangari et al., 2000]. hydrolase, UxaA family LocusTag: BRA0806 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699979.1 Gene name: galcD Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FVM8 NCBIProteinGI: 23500539 PMID: 14979322 NCBIGene: 1165248 glucose-6-phosphate 1-dehydrogenase PMID: 12761078 UniProtKB: PR:Q8FVP8 NCBIProteinGI: 23500514 Gene name: zwf This protein is a Brucella virulence factor. MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. NCBIGene: 1165220 LocusTag: BRA0778 NCBIProteinAccess:NP_699954.1 Molecule Role Annotation: MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. exodeoxyribonuclease VII large subunit NCBIProteinGI: 23500501 NCBIGene: 1165206 Molecule Role Annotation: FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. Gene name: xseA LocusTag: BRA0764 This protein is a Brucella virulence factor. FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. NCBIProteinAccess:NP_699941.1 PMID: 14638795 UniProtKB: PR:Q8FVR1 glycine cleavage system T protein Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinGI: 23500464 UniProtKB: PR:Q8FVU8 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis gcvT gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. LocusTag: BRA0727 NCBIGene: 1165169 PMID: 12438693 NCBIProteinAccess:NP_699904.1 Gene name: gcvT glycine dehydrogenase This protein is a Brucella virulence factor. FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor PMID: CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (By similarity)(Swiss-Prot: Q8FVU9). CATALYTIC ACTIVITY: Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2)(Swiss-Prot: Q8FVU9). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FVU9). SUBUNIT: The glycine cleavage system is composed of four proteins: P, T, L and H (By similarity)(Swiss-Prot: Q8FVU9). SIMILARITY: Belongs to the gcvP family(Swiss-Prot: Q8FVU9). MUTATION: gcvP encodes for glycine dehydrogenase and is required for persistent infection in mouse model [Ref6482:Ficht, 2003]. Molecule Role Annotation: FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor Gene name: gcvP NCBIProteinAccess:NP_699902.1 LocusTag: BRA0725 NCBIGene: 1165167 NCBIProteinGI: 23500462 UniProtKB: PR:Q8FVU9 SIS domain protein This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: RpiR NCBIGene: 1165154 LocusTag: BRA0712 UniProtKB: PR:Q8FVV9 NCBIProteinGI: 23500452 NCBIProteinAccess:NP_699892.1 iron compound ABC transporter, periplasmic iron compound-binding protein, putative NCBIGene: 1165142 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. LocusTag: BRA0700 Gene name: fbpA NCBIProteinAccess:NP_699880.1 NCBIProteinGI: 23500440 PMID: 14979322 UniProtKB: PR:Q8FVX0 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. sugar ABC transporter, permease protein, putative Molecule Role Annotation: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. Gene name: BRA0692 NOT ugpA NCBIGene: 1165134 This protein is a Brucella virulence factor. MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. PMID: 14638795 LocusTag: BRA0692 NCBIProteinGI: 23500433 NCBIProteinAccess:NP_699873.1 UniProtKB: PR:Q8FVX6 glycerol-3-phosphate ABC transporter, permease protein LocusTag: BRA0656 PMID: 14638795 Gene name: ugpA NCBIProteinGI: 23500400 NCBIProteinAccess:NP_699840.1 Molecule Role Annotation: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. This protein is a Brucella virulence factor. MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. NCBIGene: 1165098 UniProtKB: PR:Q8FW09 glycerol-3-phosphate ABC transporter, periplasmic glycerol-3-phosphate-binding protein NCBIGene: 1165097 NCBIProteinAccess:NP_699839.1 LocusTag: BRA0655 PMID: 16817909 UniProtKB: PR:Q8FW10 Gene name: ugpB This protein is a Brucella virulence factor. MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. Molecule Role Annotation: MUTATION: B suis ugpB mutant does not contain SP41 protein. Mutants lacking SP41 production are less invasive, but proliferate in HeLa cells. An isogenic DeltaugpB mutant showed a significant inhibitory effect on Brucella adherence and invasion of human cultured epithelial cells and this effect could be reversed by restoration of the ugpB on a plasmid. [Ref6479:Castañeda-Roldán et al., 2006]. NCBIProteinGI: 23500399 polar differentiation response regulator NCBIProteinGI: 23500356 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699796.1 LocusTag: BRA0612 NCBIGene: 1165052 Gene name: divK UniProtKB: PR:Q8FW53 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. acyl-CoA dehydrogenase family protein PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1165038 LocusTag: BRA0598 NCBIProteinAccess:NP_699782.1 Gene name: aidB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FW64 NCBIProteinGI: 23500342 phosphatidylcholine synthase NCBIGene: 1165011 LocusTag: BRA0572 NCBIProteinGI: 23500316 GenBank: AE014292 UniProtKB: PR:Q8FW88 NCBIProteinAccess:NP_699756 Molecule Role Annotation: MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. Gene name: pcs PMID: 16882035 This protein is a Brucella virulence factor. MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. ABC transporter, permease protein UniProtKB: PR:Q8FW92 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699752.1 NCBIGene: 1165007 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: rbsC LocusTag: BRA0568 NCBIProteinGI: 23500312 cytochrome d ubiquinol oxidase, subunit II UniProtKB: PR:Q8FWE4 LocusTag: BRA0511 This protein is a Brucella virulence factor. MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. Gene name: cydB NCBIGene: 1164949 NCBIProteinAccess:NP_699698.1 PMID: 11274104 NCBIProteinGI: 23500258 Molecule Role Annotation: MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6477:Endley et al., 2001]. ABC transporter, ATP-binding/permease protein NCBIGene: 1164947 LocusTag: BRA0509 NCBIProteinAccess:NP_699696.1 NCBIProteinGI: 23500256 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: cydC Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FWE6 ABC transporter, ATP-binding protein CydD NCBIProteinAccess:NP_699695.1 NCBIProteinGI: 23500255 LocusTag: BRA0508 UniProtKB: PR:Q8FWE7 Molecule Role Annotation: MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. NCBIGene: 1164946 This protein is a Brucella virulence factor. MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. Gene name: cydD PMID: 12761078 taurine ABC transporter, permease protein, putative NCBIProteinGI: 23500215 PMID: 14979322 NCBIProteinAccess:NP_699655.1 Gene name: ssuB UniProtKB: PR:Q8FWI7 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Permease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Permease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1164905 LocusTag: BRA0467 glycerol kinase NCBIProteinAccess:NP_699632.1 NCBIGene: 1164881 UniProtKB: PR:Q8FWK8 Molecule Role Annotation: FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8). CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8). PATHWAY: Glycerol utilization Gene name: glpK This protein is a Brucella virulence factor. FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8). CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8). PATHWAY: Glycerol utilization LocusTag: BRA0443 PMID: first (rate-limiting) step(Swiss-Prot: Q8FWK8). SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8). MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23500192 putative phosphoketolase LocusTag: BRA0385 NCBIProteinGI: 23500138 PMID: 14979322 UniProtKB: PR:Q8FWR0 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: xfp NCBIProteinAccess:NP_699578.1 NCBIGene: 1164823 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. transcriptional regulator OxyR NCBIProteinAccess:NP_699547 This protein is a Brucella virulence factor. MUTATION: The transcription product of Brucella abortus oxyR binds to the B abortus catalase promoter region. A gene replacementdeletion Brucella oxyR mutant exhibits increased sensitivity to prolonged exposure to H2O2 and is unable to adapt to H2O2 in the environment [Ref6476:Kim and Mayfield, 2000]. GenBank: AE014292 UniProtKB: PR:Q8FWU1 PMID: 10986275 LocusTag: BRA0354 Molecule Role Annotation: MUTATION: The transcription product of Brucella abortus oxyR binds to the B abortus catalase promoter region. A gene replacementdeletion Brucella oxyR mutant exhibits increased sensitivity to prolonged exposure to H2O2 and is unable to adapt to H2O2 in the environment [Ref6476:Kim and Mayfield, 2000]. NCBIGene: 1164792 Gene name: oxyR NCBIProteinGI: 23500107 phosphoglucomutase, putative PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BRA0348 NCBIProteinGI: 23500101 UniProtKB: PR:Q8FWU7 Gene name: manB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699541.1 NCBIGene: 1164786 mannose-1-phosphate guanylyltransferase/mannose-6-phosphate isomerase NCBIProteinAccess:NP_699540.1 LocusTag: BRA0347 NCBIGene: 1164785 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: wbpW PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FWU8 NCBIProteinGI: 23500100 glutaredoxin-like protein nrdH This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FWX8 NCBIGene: 1164751 LocusTag: BRA0314 NCBIProteinAccess:NP_699509.1 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 23500069 Gene name: nrdH respiratory nitrate reductase, alpha subunit Gene name: narG Molecule Role Annotation: MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB: PR:Q8FWZ3 This protein is a Brucella virulence factor. MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinGI: 23500054 LocusTag: BRA0299 PMID: 12438693 NCBIProteinAccess:NP_699494.1 NCBIGene: 1164736 norD protein NCBIProteinGI: 23500008 Gene name: norD NCBIProteinAccess:NP_699448.1 LocusTag: BRA0251 UniProtKB: PR:Q8FX38 PMID: 16495577 NCBIGene: 1164688 Molecule Role Annotation: MUTATION: A mutant of Brucella suis bearing a Tn5 insertion in norD , the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions (more-than-5log reduction in viable counts). As a consequence of the norD mutation , NO might not be further reduced to N2O by the NO reductase and it could become toxic for the bacteria. The infection of resting macrophages showed that the norD mutant and the wild-type strain displayed similar rates of multiplication. On the contrary, activation of J774A.1 cells by LPS and IFN was accompanied by a more-thantenfold attenuation of the norD mutant at 48 h p. i. [Ref6475:Loisel-Meyer et al., 2006]. This protein is a Brucella virulence factor. MUTATION: A mutant of Brucella suis bearing a Tn5 insertion in norD , the last gene of the operon norEFCBQD, encoding nitric oxide reductase, was unable to survive under anaerobic denitrifying conditions (more-than-5log reduction in viable counts). As a consequence of the norD mutation , NO might not be further reduced to N2O by the NO reductase and it could become toxic for the bacteria. The infection of resting macrophages showed that the norD mutant and the wild-type strain displayed similar rates of multiplication. On the contrary, activation of J774A.1 cells by LPS and IFN was accompanied by a more-thantenfold attenuation of the norD mutant at 48 h p. i. [Ref6475:Loisel-Meyer et al., 2006]. cytochrome c oxidase, subunit III UniProtKB: PR:Q8FX43 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: norE LocusTag: BRA0246 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1164683 NCBIProteinAccess:NP_699443.1 NCBIProteinGI: 23500003 CAIB/BAIF family protein NCBIGene: 1164661 LocusTag: BRA0224 NCBIProteinAccess:NP_699423.1 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8FX63 Gene name: caiB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23499983 transcriptional regulator, GntR family NCBIGene: 1164614 Gene name: gntR Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699379.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23499939 LocusTag: BRA0177 UniProtKB: PR:Q8FXA3 PMID: 14979322 flagellar basal body P-ring protein UniProtKB: PR:Q8FXC4 NCBIProteinGI: 161486704 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: P-ring [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BRA0156 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: P-ring [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: flgI NCBIProteinAccess:NP_699358.2 PMID: 14979322 NCBIGene: 1164593 transcriptional regulator, DeoR family PMID: 14979322 NCBIProteinGI: 23499909 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FXD3 NCBIProteinAccess:NP_699349.1 NCBIGene: 1164583 Gene name: deoR LocusTag: BRA0146 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. glycosyl transferase, group 2 family protein PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699338.1 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FXE4 NCBIGene: 1164572 LocusTag: BRA0135 NCBIProteinGI: 23499898 Gene name: gtrB transcriptional regulator, LuxR family Gene name: vjbR NCBIGene: 1164556 NCBIProteinAccess:NP_699323.1 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23499883 UniProtKB: PR:Q8FXF9 LocusTag: BRA0119 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. 6-phosphogluconate dehydrogenase This protein is a Brucella virulence factor. MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. PMID: 12761078 NCBIGene: 1164548 NCBIProteinAccess:NP_699316.1 UniProtKB: PR:Q8FXG6 Molecule Role Annotation: MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. Gene name: gnd NCBIProteinGI: 23499876 LocusTag: BRA0111 type IV secretion system protein VirB11 PMID: 15312849 This protein is a Brucella virulence factor. MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. LocusTag: BRA0059 GenBank: AE014292 NCBIProteinGI: 23499826 Gene name: virB11 NCBIProteinAccess:NP_699266 Molecule Role Annotation: MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. NCBIGene: 1164496 UniProtKB: PR:Q8FXK7 glutamate synthase subunit beta NCBIGene: 1164492 UniProtKB: PR:Q8FXL0 Molecule Role Annotation: MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. This protein is a Brucella virulence factor. MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. NCBIProteinAccess:NP_699262.1 NCBIProteinGI: 23499822 LocusTag: BRA0055 PMID: 10858227 Gene name: gltD sensor histidine kinase UniProtKB: PR:Q8FXM4 Gene name: nodV LocusTag: BRA0041 NCBIProteinGI: 23499808 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699248.1 NCBIGene: 1164477 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 magnesium ion-transporting ATPase, E1-E2 family PMID: 14979322 NCBIProteinGI: 23499804 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_699244.1 LocusTag: BRA0037 NCBIGene: 1164473 UniProtKB: PR:Q8FXM8 Gene name: mgtB ribokinase, putative This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinAccess:NP_699212.1 Gene name: rbsK UniProtKB: PR:Q8FXR0 NCBIGene: 1164441 LocusTag: BRA0005 NCBIProteinGI: 23499772 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. formamidopyrimidine-DNA glycosylase Molecule Role Annotation: FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6). SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6). SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6). SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6). MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIGene: 1167886 UniProtKB: PR:Q8FXR6 NCBIProteinAccess:NP_699157.1 Gene name: mutM LocusTag: BR2183 NCBIProteinGI: 23503030 This protein is a Brucella virulence factor. FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6). SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6). SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6). SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6). MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. phospholipid N-methyltransferase NCBIGene: 1167830 PMID: 16882035 This protein is a Brucella virulence factor. MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. NCBIProteinAccess:NP_699102 Molecule Role Annotation: MUTATION: The role of Phosphatidylcholine (PC) in Brucella abortus was examined by generating mutants in pcs (BApcs) and pmtA (BApmtA), which encode key enzymes of the two bacterial PC biosynthetic routes, the choline and methyl-transferase pathways. In rich medium, BApcs and the double mutant BApcspmtA but not BApmtA displayed reduced growth, increased phosphatidylethanolamine and no PC, showing that Pcs is essential for PC synthesis under these conditions. In minimal medium, the parental strain, BApcs and BApmtA showed reduced but significant amounts of PC suggesting that PmtA may also be functional Probing with phage Tb, antibiotics, polycations and serum demonstrated that all mutants had altered envelopes. In macrophages, BApcs and BApcspmtA showed reduced ability to evade fusion with lysosomes and establish a replication niche. In mice, BApcs showed attenuation only at early times after infection, BApmtA at later stages and BApcspmtA throughout. The results suggest that Pcs and PmtA have complementary roles in vivo related to nutrient availability and that PC and the membrane properties that depend on this typical eukaryotic phospholipid are essential for Brucella virulence [Ref6478:Conde-Alvarez et al., 2006]. UniProtKB: PR:Q8FXX0 NCBIProteinGI: 23502975 GenBank: AE014291 Gene name: pmtA LocusTag: BR2127 molecular chaperone DnaK Gene name: dnaK NCBIProteinGI: 23502973 PMID: 11854256 LocusTag: BR2125 NCBIProteinAccess:NP_699100.1 Molecule Role Annotation: FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2). INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2). SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2). MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. UniProtKB: PR:Q8FXX2 This protein is a Brucella virulence factor. FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2). INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2). SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2). MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. NCBIGene: 1167828 sensor histidine kinase BvrS, putative NCBIProteinGI: 23502939 NCBIProteinAccess:NP_699066.1 NCBIGene: 1167794 UniProtKB: PR:Q8FY03 This protein is a Brucella virulence factor. MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. LocusTag: BR2091 Molecule Role Annotation: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. PMID: 12218183 Gene name: bvrS DNA-binding response regulator BvrR, putative NCBIGene: 1167793 NCBIProteinGI: 23502938 NCBIProteinAccess:NP_699065.1 PMID: 12218183 Molecule Role Annotation: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. LocusTag: BR2090 UniProtKB: PR:Q8FY04 Gene name: bvrR This protein is a Brucella virulence factor. MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6499:Guzman-Verri et al., 2002]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6499:Guzman-Verri et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6499:Guzman-Verri et al., 2002]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6499:Guzman-Verri et al., 2002]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6499:Guzman-Verri et al., 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. imidazole glycerol phosphate synthase subunit HisF NCBIProteinAccess:NP_699060.1 UniProtKB: PR:Q8FY07 LocusTag: BR2085 This protein is a Brucella virulence factor. FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 23502933 Molecule Role Annotation: FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis NCBIGene: 1167788 PMID: L-histidine biosynthesis Gene name: hisF histidinol-phosphate aminotransferase LocusTag: BR1987 PMID: L-histidine biosynthesis NCBIGene: 1167688 Gene name: hisC NCBIProteinAccess:NP_698962.1 Molecule Role Annotation: CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98). PATHWAY: Amino-acid biosynthesis This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate(Swiss-Prot: Q8FY98). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8FY98). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 23502835 UniProtKB: PR:Q8FY98 hypoxanthine-guanine phosphoribosyltransferase NCBIProteinAccess:NP_698960.1 NCBIGene: 1167686 NCBIProteinGI: 23502833 LocusTag: BR1985 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FYA0 Gene name: hpt Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. diaminopimelate decarboxylase This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: lysA UniProtKB: PR:Q8FYA2 PMID: 12438693 NCBIProteinAccess:NP_698958.1 NCBIGene: 1167684 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinGI: 23502831 LocusTag: BR1983 isopropylmalate isomerase large subunit Molecule Role Annotation: FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis This protein is a Brucella virulence factor. FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 23502757 NCBIProteinAccess:NP_698884.1 PMID: L-leucine biosynthesis Gene name: leuC NCBIGene: 1167606 UniProtKB: PR:Q8FYG9 LocusTag: BR1906 branched-chain amino acid ABC transporter, permease protein UniProtKB: PR:Q8FYS1 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. LocusTag: BR1791 NCBIProteinGI: 23502645 NCBIProteinAccess:NP_698772.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1167484 Gene name: livH PMID: 14979322 pyruvate carboxylase NCBIProteinGI: 23502636 LocusTag: BR1781 This protein is a Brucella virulence factor. MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. Gene name: pyc NCBIProteinAccess:NP_698763.1 NCBIGene: 1167474 Molecule Role Annotation: MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. PMID: 10678941 UniProtKB: PR:Q8FYT0 phosphoribosylaminoimidazole carboxylase, catalytic subunit NCBIProteinGI: 23502601 NCBIProteinAccess:NP_698728.1 Gene name: purE NCBIGene: 1167437 PMID: IMP biosynthesis Molecule Role Annotation: FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3). CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3). PATHWAY: Nucleotide biosynthesis LocusTag: BR1744 UniProtKB: PR:Q8FYW3 This protein is a Brucella virulence factor. FUNCTION: This subunit can alone transform AIR to CAIR, but in association with purK, which possesses an ATPase activity, an enzyme complex is produced which is capable of converting AIR to CAIR efficiently under physiological condition (By similarity)(Swiss-Prot: Q8FYW3). CATALYTIC ACTIVITY: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO(2)(Swiss-Prot: Q8FYW3). PATHWAY: Nucleotide biosynthesis transcriptional regulator, AsnC family NCBIProteinAccess:NP_698661.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BR1676 NCBIGene: 1167369 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8FZ27 Gene name: ansC NCBIProteinGI: 23502534 HlyD family secretion protein NCBIProteinAccess:NP_698656.1 LocusTag: BR1671 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1167364 UniProtKB: PR:Q8FZ29 NCBIProteinGI: 23502529 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: macA base-excision DNA repair protein LocusTag: BR1646 NCBIGene: 1167338 NCBIProteinAccess:NP_698633.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FZ51 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 23502506 Gene name: alkA disulfide bond formation protein B, putative LocusTag: BR1642 PMID: 14979322 NCBIGene: 1167334 Gene name: dsbB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8FZ55 NCBIProteinGI: 23502502 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_698629.1 2-isopropylmalate synthase Gene name: leuA NCBIGene: 1167249 Molecule Role Annotation: FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis UniProtKB: PR:Q8FZC4 NCBIProteinAccess:NP_698557.2 NCBIProteinGI: 161486694 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis LocusTag: BR1566 PMID: L-leucine biosynthesis transcriptional regulator, LysR family Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23502367 Gene name: lysR PMID: 14979322 NCBIGene: 1167181 LocusTag: BR1498 UniProtKB: PR:Q8FZI3 NCBIProteinAccess:NP_698494.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. aspartate aminotransferase Molecule Role Annotation: MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. This protein is a Brucella virulence factor. MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. NCBIProteinGI: 23502364 PMID: 12761078 LocusTag: BR1495 UniProtKB: PR:Q8FZI6 NCBIGene: 1167178 Gene name: aspC NCBIProteinAccess:NP_698491.1 hypothetical protein PMID: 12761078, 15135535 NCBIProteinGI: 23502334 Gene name: pncA LocusTag: BR1465 UniProtKB: PR:Q8FZL5 This protein is a Brucella virulence factor. MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. Molecule Role Annotation: MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. NCBIProteinAccess:NP_698461.1 NCBIGene: 1167147 pyrazinamidase/nicotinamidase NCBIProteinGI: 23502333 PMID: 12761078 LocusTag: BR1464 Gene name: pncA NCBIProteinAccess:NP_698460.1 NCBIGene: 1167146 UniProtKB: PR:Q8FZL6 Molecule Role Annotation: MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6469:Kim et al., 2003]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6469:Kim et al., 2003]. It indicates that the mutant has reduced virulence in mice. This protein is a Brucella virulence factor. MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6469:Kim et al., 2003]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6469:Kim et al., 2003]. It indicates that the mutant has reduced virulence in mice. phosphoserine phosphatase Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. LocusTag: BR1391 NCBIProteinGI: 23502262 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. PMID: 12438693 NCBIProteinAccess:NP_698389.1 Gene name: serB NCBIGene: 1167073 UniProtKB: PR:Q8FZT1 ketol-acid reductoisomerase UniProtKB: PR:Q8FZU1 Gene name: ilvC PMID: L-isoleucine biosynthesis This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). PATHWAY: Amino-acid biosynthesis NCBIProteinAccess:NP_698378.1 Molecule Role Annotation: CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). PATHWAY: Amino-acid biosynthesis NCBIGene: 1167062 LocusTag: BR1380 NCBIProteinGI: 23502251 aminotransferase, class I NCBIProteinAccess:NP_698376.1 PMID: 14979322 NCBIProteinGI: 23502249 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1167060 UniProtKB: PR:Q8FZU3 LocusTag: BR1378 Gene name: aspB cobyrinic acid a,c-diamide synthase PMID: 14638795 LocusTag: BR1296 UniProtKB: PR:Q8G020 Molecule Role Annotation: FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020). PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020). SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020). MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. NCBIProteinGI: 23502172 NCBIGene: 1166977 This protein is a Brucella virulence factor. FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020). PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020). SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020). MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. Gene name: cobB NCBIProteinAccess:NP_698299.1 lactoylglutathione lyase NCBIProteinAccess:NP_698271.1 LocusTag: BR1268 Gene name: gloA UniProtKB: PR:Q8G047 NCBIProteinGI: 23502144 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1166947 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 DNA-directed RNA polymerase subunit alpha LocusTag: BR1209 UniProtKB: PR:Q8G094 NCBIProteinAccess:NP_698213.1 NCBIGene: 1166885 This protein is a Brucella virulence factor. FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. PMID: 14638795 Molecule Role Annotation: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. Gene name: rpoA NCBIProteinGI: 23502086 undecaprenyl diphosphate synthase Molecule Role Annotation: FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9). CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9). COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9). SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinGI: 23502036 This protein is a Brucella virulence factor. FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9). CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9). COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9). SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. LocusTag: BR1158 PMID: 12438693 Gene name: uppS UniProtKB: PR:Q8G0D9 NCBIGene: 1166834 NCBIProteinAccess:NP_698163.1 rotamase family protein NCBIGene: 1166815 PMID: 14979322 UniProtKB: PR:Q8G0F6 NCBIProteinGI: 23502017 Gene name: ppiD LocusTag: BR1139 NCBIProteinAccess:NP_698144.1 Molecule Role Annotation: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004]. FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004]. FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. nitrogen regulation protein NtrC PMID: 10373105 This protein is a Brucella virulence factor. MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. Molecule Role Annotation: MUTATION: ntrC encodes for a response regulator subfamily (NtrC). A B suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue [Ref6496:Dorrell et al., 1999]. NCBIProteinAccess:NP_698122.1 UniProtKB: PR:Q8G0H7 NCBIProteinGI: 23501995 Gene name: ntrC LocusTag: BR1117 NCBIGene: 1166793 nitrogen regulation protein NtrY Gene name: ntrY This protein is a Brucella virulence factor. MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. UniProtKB: PR:Q8G0H8 NCBIProteinGI: 23501994 PMID: 10678941 Molecule Role Annotation: MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. LocusTag: BR1116 NCBIGene: 1166792 NCBIProteinAccess:NP_698121.1 ATP-dependent protease La LocusTag: BR1106 NCBIGene: 1166782 Molecule Role Annotation: FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7). CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7). SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7). SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7). MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. NCBIProteinAccess:NP_698111.1 Gene name: lon NCBIProteinGI: 23501984 PMID: 10672180 This protein is a Brucella virulence factor. FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7). CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7). SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7). SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7). MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. UniProtKB: PR:Q8G0I7 excinuclease ABC subunit A PMID: 16816190 NCBIProteinGI: 23501982 UniProtKB: PR:Q8G0I9 NCBIProteinAccess:NP_698109.1 LocusTag: BR1104 NCBIGene: 1166780 Gene name: uvrA Molecule Role Annotation: FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. This protein is a Brucella virulence factor. FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. CAIB/BAIF family protein Gene name: caiB LocusTag: BR1084 PMID: 14979322 UniProtKB: PR:Q8G0K8 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_698089.1 NCBIGene: 1166760 NCBIProteinGI: 23501962 cysteine synthase A PMID: 14979322 NCBIProteinGI: 23501931 NCBIGene: 1166727 NCBIProteinAccess:NP_698058.1 Gene name: cysK This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8G0N6 LocusTag: BR1053 glutamine synthetase, type I UniProtKB: PR:Q8G0T3 NCBIGene: 1166677 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: glnA PMID: 12438693 NCBIProteinAccess:NP_698011.1 NCBIProteinGI: 23501884 LocusTag: BR1004 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. glycosyl transferase, group 1 family protein NCBIGene: 1166655 PMID: 14979322 LocusTag: BR0982 Gene name: wbdA This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23501863 NCBIProteinAccess:NP_697990.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8G0V3 amino acid ABC transporter, periplasmic amino acid-binding protein NCBIGene: 1166625 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8G0X7 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_697965.1 NCBIProteinGI: 23501838 Gene name: artI PMID: 14979322 LocusTag: BR0955 hypothetical protein LocusTag: BR0933 UniProtKB: PR:Q8G0Z8 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23501817 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: dsbA NCBIGene: 1166602 PMID: 14979322 NCBIProteinAccess:NP_697944.1 cysteine desulfurase, putative UniProtKB: PR:Q8G101 NCBIGene: 1166599 LocusTag: BR0930 NCBIProteinAccess:NP_697941.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004]. FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: nifS Molecule Role Annotation: FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004]. FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23501814 PMID: 14979322 N-acetylmuramoyl-L-alanine amidase, family 3 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BR0915 Gene name: amiC NCBIGene: 1166584 NCBIProteinAccess:NP_697928.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23501801 UniProtKB: PR:Q8G113 outer membrane protein, putative PMID: 14979322 NCBIProteinGI: 23501795 LocusTag: BR0909 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: dsbA NCBIGene: 1166578 UniProtKB: PR:Q8G119 NCBIProteinAccess:NP_697922.1 trigger factor UniProtKB: PR:Q8G129 NCBIGene: 1166567 This protein is a Brucella virulence factor. FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. Molecule Role Annotation: FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. NCBIProteinAccess:NP_697911.1 LocusTag: BR0898 Gene name: tig PMID: 14638795 NCBIProteinGI: 23501784 phosphoribosylformylglycinamidine synthase II NCBIProteinGI: 23501724 Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183). PATHWAY: Nucleotide biosynthesis LocusTag: BR0837 PMID: IMP biosynthesis Gene name: purL UniProtKB: PR:Q8G183 NCBIGene: 1166505 NCBIProteinAccess:NP_697851.1 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183). PATHWAY: Nucleotide biosynthesis serine hydroxymethyltransferase LocusTag: BR0765 NCBIProteinAccess:NP_697779.1 PMID: 12438693 This protein is a Brucella virulence factor. FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: glyA NCBIProteinGI: 23501652 UniProtKB: PR:Q8G1F1 NCBIGene: 1166430 Molecule Role Annotation: FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. epimerase/dehydratase family protein, putative UniProtKB: PR:Q8G1K0 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: galE LocusTag: BR0715 NCBIGene: 1166378 NCBIProteinAccess:NP_697729.1 NCBIProteinGI: 23501602 phosphoribosylaminoimidazole synthetase This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis UniProtKB: PR:Q8G1K5 NCBIProteinGI: 23501597 Gene name: purM PMID: IMP biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis LocusTag: BR0710 NCBIGene: 1166373 NCBIProteinAccess:NP_697724.1 aminopeptidase N This protein is a Brucella virulence factor. MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. LocusTag: BR0617 NCBIGene: 1166279 NCBIProteinGI: 23501504 Gene name: pepN Molecule Role Annotation: MUTATION: A single mutation of PepN leads to a significant decrease in the growth rate, thus PepN seems to play a more prominent role than do the other proteases [Ref6491:Contreras-Rodriguez et al., 2003]. NCBIProteinAccess:NP_697631.1 PMID: 12933870 UniProtKB: PR:Q8G1T7 hypothetical protein UniProtKB: PR:Q8G1T9 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_697629.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: lpsA LocusTag: BR0615 PMID: 14979322 NCBIGene: 1166277 NCBIProteinGI: 23501502 sensor histidine kinase PMID: 14979322 LocusTag: BR0605 NCBIGene: 1166267 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_697619.1 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23501492 UniProtKB: PR:Q8G1U8 Gene name: feuQ DNA-binding response regulator LocusTag: BR0604 NCBIProteinGI: 23501491 NCBIGene: 1166266 NCBIProteinAccess:NP_697618.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: feuP UniProtKB: PR:Q8G1U9 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. glycosyl transferase, group 1 family protein This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8G211 NCBIProteinAccess:NP_697556.1 NCBIGene: 1166202 LocusTag: BR0540 NCBIProteinGI: 23501429 Gene name: wbpZ PMID: 14979322 phosphomannomutase, putative This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1166199 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BR0537 NCBIProteinGI: 23501426 PMID: 14979322 NCBIProteinAccess:NP_697553.1 UniProtKB: PR:Q8G214 Gene name: pmm mannosyltransferase, putative LocusTag: BR0529 NCBIProteinAccess:NP_697548.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 23501421 UniProtKB: PR:Q8G218 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1166191 Gene name: wbkA GDP-mannose 4,6-dehydratase This protein is a Brucella virulence factor. MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. Gene name: gmd Molecule Role Annotation: MUTATION: gmd may be involved in perosamine synthesis. It has been shown to be in LPS synthesis since its B. melitensis mutation induces rough phenotype [Ref6490:Moriyón et al., 2004]. PMID: 15099501 NCBIProteinGI: 23501417 NCBIGene: 1166184 LocusTag: BR0522 NCBIProteinAccess:NP_697544.1 UniProtKB: PR:Q8G219 perosamine synthase, putative UniProtKB: PR:Q8G220 LocusTag: BR0521 NCBIGene: 1166183 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 23501416 Gene name: perA NCBIProteinAccess:NP_697543.1 O-antigen export system permease protein RfbD This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8G221 Gene name: rfbD NCBIProteinAccess:NP_697542.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 23501415 LocusTag: BR0520 NCBIGene: 1166182 wbkB protein Molecule Role Annotation: MUTATION: No function has been assigned to the B. melitensis 16M wbkB gene either by homology search or functionally, because deletion of wbkB did not interfere with the O-antigen structure [Ref6489:Godfroid et al., 2000]. PMID: 11081580 GenBank: AE014291 NCBIProteinGI: 23501413 NCBIProteinAccess:NP_697540 This protein is a Brucella virulence factor. MUTATION: No function has been assigned to the B. melitensis 16M wbkB gene either by homology search or functionally, because deletion of wbkB did not interfere with the O-antigen structure [Ref6489:Godfroid et al., 2000]. NCBIGene: 1166180 LocusTag: BR0518 UniProtKB: PR:Q8G223 Gene name: wbkB glycosyl transferase, group 4 family protein This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BR0511 NCBIGene: 1166172 UniProtKB: PR:Q8G225 NCBIProteinGI: 23501411 NCBIProteinAccess:NP_697538.1 Gene name: wbpL twin-arginine translocation signal domain protein UniProtKB: PR:Q8G237 NCBIProteinGI: 23501397 Gene name: dsbA This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BR0496 NCBIProteinAccess:NP_697524.1 PMID: 14979322 NCBIGene: 1166157 threonine synthase PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BR0484 NCBIProteinGI: 23501385 NCBIProteinAccess:NP_697512.1 Gene name: thrC UniProtKB: PR:Q8G249 NCBIGene: 1166145 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. tldD protein, putative NCBIProteinAccess:NP_697493.1 NCBIProteinGI: 23501366 UniProtKB: PR:Q8G266 Gene name: tldD LocusTag: BR0465 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1166126 amidophosphoribosyltransferase UniProtKB: PR:Q8G282 This protein is a Brucella virulence factor. MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. NCBIGene: 1166107 Molecule Role Annotation: MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. Gene name: purF NCBIProteinGI: 23501347 PMID: 12761078 LocusTag: BR0446 NCBIProteinAccess:NP_697474.1 ABC transporter, ATP-binding/permease protein UniProtKB: PR:Q8G286 NCBIGene: 1166103 NCBIProteinGI: 23501343 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. LocusTag: BR0442 NCBIProteinAccess:NP_697470.1 Gene name: exsA phosphoribosylamine--glycine ligase NCBIProteinAccess:NP_697444.1 NCBIProteinGI: 23501317 UniProtKB: PR:Q8G2B1 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis LocusTag: BR0414 Gene name: purD Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis PMID: IMP biosynthesis NCBIGene: 1166075 transport protein PMID: 10741969 NCBIProteinGI: 23501276 NCBIProteinAccess:NP_697403.1 NCBIGene: 1166033 LocusTag: BR0372 Gene name: bacA Molecule Role Annotation: MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. This protein is a Brucella virulence factor. MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6487:LeVier et al., 2000]. UniProtKB: PR:Q8G2F1 sensor histidine kinase/response regulator PMID: 14979322 UniProtKB: PR:Q8G2K3 LocusTag: BR0316 NCBIProteinGI: 23501223 Gene name: vsrB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_697350.1 NCBIGene: 1165977 dihydroorotate dehydrogenase 2 LocusTag: BR0311 Molecule Role Annotation: MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. UniProtKB: PR:Q8G2K8 NCBIProteinGI: 23501218 NCBIGene: 1165972 Gene name: pyrD PMID: 12761078 This protein is a Brucella virulence factor. MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. NCBIProteinAccess:NP_697345.1 glucose-6-phosphate isomerase PMID: glycolysis This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation Molecule Role Annotation: CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation NCBIProteinGI: 23501192 NCBIGene: 1165946 UniProtKB: PR:Q8G2N3 Gene name: pgi NCBIProteinAccess:NP_697319.1 LocusTag: BR0285 histidinol dehydrogenase Molecule Role Annotation: FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis Gene name: hisD NCBIGene: 1165911 UniProtKB: PR:Q8G2R2 PMID: L-histidine biosynthesis This protein is a Brucella virulence factor. FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 23501159 LocusTag: BR0252 NCBIProteinAccess:NP_697286.1 sugar ABC transporter, ATP-binding protein NCBIProteinGI: 23501145 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_697272.1 UniProtKB: PR:Q8G2S6 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BR0238 NCBIGene: 1165896 Gene name: malK B12-dependent methionine synthase Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: metH NCBIProteinGI: 23501099 LocusTag: BR0188 NCBIProteinAccess:NP_697226.1 PMID: 14979322 NCBIGene: 1165845 UniProtKB: PR:Q8G2X1 sulfite reductase (NADPH) hemoprotein beta-component PMID: 14979322 LocusTag: BR0181 NCBIProteinAccess:NP_697219.1 NCBIGene: 1165838 UniProtKB: PR:Q8G2X8 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 23501092 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. Gene name: cysI PII uridylyl-transferase Molecule Role Annotation: FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312). CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312). SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312). MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. NCBIGene: 1165801 This protein is a Brucella virulence factor. FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312). CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312). SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312). MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. NCBIProteinGI: 23501056 UniProtKB: PR:Q8G312 Gene name: glnD PMID: 10678941 LocusTag: BR0144 NCBIProteinAccess:NP_697183.1 cyclic beta 1-2 glucan synthetase PMID: 14979322 Gene name: ndvB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BR0111 NCBIProteinGI: 23501025 NCBIProteinAccess:NP_697152.1 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8G341 NCBIGene: 1165768 dihydroxy-acid dehydratase PMID: L-isoleucine biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 23501013 Gene name: ilvD LocusTag: BR0099 NCBIProteinAccess:NP_697140.1 NCBIGene: 1165756 UniProtKB: PR:Q8G353 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis phosphoglucomutase NCBIGene: 1165715 NCBIProteinGI: 23500973 Molecule Role Annotation: MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. LocusTag: BR0058 Gene name: pgm PMID: 10992476 UniProtKB: PR:Q8G392 This protein is a Brucella virulence factor. MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6486:Ugalde et al., 2000]. NCBIProteinAccess:NP_697100.1 prephenate dehydratase Gene name: pheA NCBIProteinAccess:NP_697079.1 This protein is a Brucella virulence factor. MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. Molecule Role Annotation: MUTATION: The product of pheA gene is specifically dedicated to the biosynthesis of phenylalanine. The B. abortus pheA mutant with mini-Tn5 disruption displays nutritional defects in vitro. Experimental findings with the B abortus ilvD, trpB, and pheA mutants suggest that tryptophan and phenylalanine are available to the brucellae in their intracellular niche but that other amino acids (eg, leucine, isoleucine, or valine) are not. The pheA::miniTn5 mutant displayed attenuation in macrophages but not in mice [Ref6485:Alcantara et al., 2004]. NCBIGene: 1165694 UniProtKB: PR:Q8G3B3 NCBIProteinGI: 23500952 LocusTag: BR0037 PMID: 15271960 30S ribosomal protein S1 NCBIGene: 1165684 PMID: 10678941 LocusTag: BR0027 UniProtKB: PR:Q8G3C2 Gene name: rpsA NCBIProteinGI: 23500942 Molecule Role Annotation: MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. This protein is a Brucella virulence factor. MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. NCBIProteinAccess:NP_697069.1 6-phosphogluconate dehydrogenase UniProtKB: PR:Q8YAX7 LocusTag: BMEII1124 This protein is a Brucella virulence factor. MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. NCBIProteinGI: 17989469 NCBIGene: 1198896 Gene name: gnd NCBIProteinAccess:NP_542102.1 Molecule Role Annotation: MUTATION: gnd is involved in pentose phosphate pathway. It is essential for intracellular growth inside HeLa cells as shown by its Brucella suis miniTn5Km2 transposon mutation analysis. The mutant is attenuated in the mouse model [Ref6469:Kim et al., 2003]. PMID: 12761078 TRANSCRIPTIONAL ACTIVATOR, LUXR FAMILY PMID: 14979322 NCBIGene: 1198888 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_542094.1 Gene name: vjbR UniProtKB: PR:Q8YAY5 NCBIProteinGI: 17989461 LocusTag: BMEII1116 BACTOPRENOL GLUCOSYL TRANSFERASE / BACTOPRENOL APOLIPOPROTEIN N-ACYLTRANSFERASE Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YB00 NCBIGene: 1198873 PMID: 14979322 LocusTag: BMEII1101 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: glycosyl transerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17989446 NCBIProteinAccess:NP_542079.1 Gene name: gtrB GLYCEROL-3-PHOSPHATE REGULON REPRESSOR PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: deoR NCBIGene: 1198865 NCBIProteinGI: 17989438 LocusTag: BMEII1093 NCBIProteinAccess:NP_542071.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YB08 flagellar basal body P-ring protein LocusTag: BMEII1084 NCBIProteinAccess:NP_542062.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: P-ring [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YB17 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: P-ring [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198856 NCBIProteinGI: 17989429 PMID: 14979322 Gene name: flgI PYRUVATE DEHYDROGENASE COMPLEX REPRESSOR LocusTag: BMEII1066 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_542044.1 Gene name: gntR NCBIProteinGI: 17989411 PMID: 14979322 UniProtKB: PR:Q8YB35 NCBIGene: 1198838 GLUCOSE/GALACTOSE TRANSPORTER This protein is a Brucella virulence factor. FUNCTION: Intake of glucose and galactose (Potential)(Swiss-Prot: Q8YB48). SUBCELLULAR LOCATION: Inner membrane UniProtKB: PR:Q8YB48 NCBIGene: 1198825 LocusTag: BMEII1053 PMID: multi-pass membrane protein (Probable)(Swiss-Prot: Q8YB48). SIMILARITY: Belongs to the major facilitator superfamily. FHS transporter (TC 2.A.1.7) family(Swiss-Prot: Q8YB48). MUTATION: B suis and maybe B canis seem to have two glucosegalactose transporters: gluP and gguAB. B abortus may express only gluP, which may explain why gluP mutants fail to survive long periods in the mouse [Ref6474:Essenberg et al., 2002]. Molecule Role Annotation: FUNCTION: Intake of glucose and galactose (Potential)(Swiss-Prot: Q8YB48). SUBCELLULAR LOCATION: Inner membrane NCBIProteinAccess:NP_542031.1 Gene name: gluP NCBIProteinGI: 17989398 HAD superfamily protein involved in N-acetyl-glucosamine catabolism Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198817 UniProtKB: PR:Q8YB55 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17989390 NCBIProteinAccess:NP_542023.1 LocusTag: BMEII1045 Gene name: BMEII1045 ZINC PROTEASE Gene name: BMEII1037 LocusTag: BMEII1037 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: Zinc protease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17989382 NCBIProteinAccess:NP_542015.1 Molecule Role Annotation: FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: Zinc protease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8YB63 NCBIGene: 1198809 NORE PROTEIN This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: norE LocusTag: BMEII1001 UniProtKB: PR:Q8YB99 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Nitric oxide reduction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_541979.1 NCBIProteinGI: 17989346 PMID: 14979322 NCBIGene: 1198773 NITRATE REDUCTASE ALPHA CHAIN UniProtKB: PR:Q8YBF0 LocusTag: BMEII0950 This protein is a Brucella virulence factor. MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1198722 Gene name: narG Molecule Role Annotation: MUTATION: The narG gene encodes for an essential component of the dissimilatory nitrate reductase complex. This complex is encoded by the narGHIJ locus, which is present in the B suis genome together with the gene of the nitrite extrusion protein, narK. The narG mutant was unable to produce nitrite from nitrate [Ref412:Kohler et al., 2002]. A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis xx gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIProteinAccess:NP_541928.1 NCBIProteinGI: 17989295 PMID: 12438693 NICKEL RESISTANCE PROTEIN PMID: 14979322 LocusTag: BMEII0935 UniProtKB: PR:Q8YBG5 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Bacterial protein of unknown function (DUF89) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17989280 NCBIProteinAccess:NP_541913.1 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Bacterial protein of unknown function (DUF89) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198707 Gene name: BMEII0935 GLUTAREDOXIN This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1198704 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Ribonucleotide recuctase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa, but not in Macrophages, mice [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17989277 UniProtKB: PR:Q8YBG8 LocusTag: BMEII0932 NCBIProteinAccess:NP_541910.1 Gene name: nrdH SPERMIDINE/PUTRESCINE-BINDING PERIPLASMIC PROTEIN UniProtKB: PR:Q8YBH7 PMID: 14979322 NCBIProteinGI: 17989268 LocusTag: BMEII0923 NCBIProteinAccess:NP_541901.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. Gene name: BMEII0923 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1198695 MANNOSE-6-PHOSPHATE ISOMERASE / MANNOSE-1-PHOSPHATE GUANYLYL TRANSFERASE (GDP) UniProtKB: PR:Q8YBK0 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: wbpW PMID: 14979322 NCBIGene: 1198672 NCBIProteinGI: 17989245 LocusTag: BMEII0900 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_541878.1 PHOSPHOMANNOMUTASE LocusTag: BMEII0899 NCBIProteinAccess:NP_541877.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198671 Gene name: manB NCBIProteinGI: 17989244 UniProtKB: PR:Q8YBK1 putative phosphoketolase Gene name: xfp UniProtKB: PR:Q8YBL8 NCBIProteinAccess:NP_541859.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BMEII0881 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Degradation [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. degradation [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198653 NCBIProteinGI: 17989226 GLYCEROL KINASE NCBIGene: 1198595 UniProtKB: PR:Q8YBR2 NCBIProteinGI: 17989168 Gene name: glpK LocusTag: BMEII0823 PMID: first (rate-limiting) step(Swiss-Prot: Q8FWK8). SIMILARITY: Belongs to the FGGY kinase family(Swiss-Prot: Q8FWK8). MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8). CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8). PATHWAY: Glycerol utilization NCBIProteinAccess:NP_541801.1 Molecule Role Annotation: FUNCTION: Key enzyme in the regulation of glycerol uptake and metabolism(Swiss-Prot: Q8FWK8). CATALYTIC ACTIVITY: ATP + glycerol = ADP + sn-glycerol 3-phosphate(Swiss-Prot: Q8FWK8). PATHWAY: Glycerol utilization NITRATE TRANSPORT PERMEASE PROTEIN NRTB NCBIProteinAccess:NP_541777.1 NCBIGene: 1198571 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Permease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17989144 LocusTag: BMEII0799 UniProtKB: PR:Q8YBT7 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Permease [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. Gene name: ssuB PMID: 14979322 TRANSPORT ATP-BINDING PROTEIN CYDD UniProtKB: PR:Q8YBX4 NCBIGene: 1198534 Molecule Role Annotation: MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. NCBIProteinGI: 17989107 This protein is a Brucella virulence factor. MUTATION: The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. PMID: 12761078 Gene name: cydD LocusTag: BMEII0762 NCBIProteinAccess:NP_541740.1 TRANSPORT ATP-BINDING PROTEIN CYDC Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: cydC UniProtKB: PR:Q8YBX5 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Cytochrome oxidase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0761 NCBIProteinAccess:NP_541739.1 NCBIProteinGI: 17989106 NCBIGene: 1198533 CYTOCHROME D UBIQUINOL OXIDASE SUBUNIT II This protein is a Brucella virulence factor. MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. Molecule Role Annotation: MUTATION: cydB is a gene that is part of the cydAB operon encoding cytochrome bd oxidase , which catalyzes an alternate terminal electron transport step in bacterial respiration. Transposon (Tn5) mutagenesis of B abortus cydB was severely attenuated for intracellular survival. Unlike the virulent strain 2308, the Brucella cydB::Tn5 mutant was severely compromised for survival in the spleens of inoculated mice [Ref6477:Endley et al., 2001]. The cydB and cydD mutants are also defective for the intracellular growth of B abortus and B suis, suggesting that functional cytochrome bd oxidase is required for growth in an intracellular environment [Ref6469:Kim et al., 2003]. PMID: 11274104, 12761078 LocusTag: BMEII0759 NCBIProteinAccess:NP_541737.1 NCBIProteinGI: 17989104 NCBIGene: 1198531 UniProtKB: PR:Q8YBX7 Gene name: cydB RIBOSE TRANSPORT SYSTEM PERMEASE PROTEIN RBSC Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: rbsC NCBIGene: 1198473 NCBIProteinGI: 17989046 PMID: 14979322 LocusTag: BMEII0701 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_541679.1 UniProtKB: PR:Q8YC31 ACYL-COA DEHYDROGENASE LocusTag: BMEII0671 NCBIProteinGI: 17989016 NCBIGene: 1198443 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: Protection against alkylation damage to DNA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: aidB UniProtKB: PR:Q8YC61 PMID: 14979322 NCBIProteinAccess:NP_541649.1 dihydroorotase LocusTag: BMEII0669 NCBIProteinAccess:NP_541647.1 Gene name: pyrC UniProtKB: PR:Q8YC63 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198441 NCBIProteinGI: 17989014 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. TWO COMPONENT RESPONSE REGULATOR PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. Gene name: divK UniProtKB: PR:Q8YC73 NCBIProteinAccess:NP_541637.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Response regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0659 NCBIProteinGI: 17989004 NCBIGene: 1198431 MEMBRANE DIPEPTIDASE This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptidase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8YCA6 NCBIProteinGI: 17988971 LocusTag: BMEII0626 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptidase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: BMEII0626 NCBIGene: 1198398 NCBIProteinAccess:NP_541604.1 SUGAR TRANSPORT SYSTEM PERMEASE PROTEIN NCBIProteinGI: 17988936 This protein is a Brucella virulence factor. MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. PMID: 14638795 Gene name: BMEII0591 NOT ugpA Molecule Role Annotation: MUTATION: UgpA is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. LocusTag: BMEII0591 NCBIGene: 1198363 NCBIProteinAccess:NP_541569.1 UniProtKB: PR:Q8YCE1 IRON(III)-BINDING PERIPLASMIC PROTEIN PRECURSOR UniProtKB: PR:Q8YCE7 Gene name: fbpA LocusTag: BMEII0584 NCBIProteinGI: 17988929 NCBIProteinAccess:NP_541562.1 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Fe3+ binding [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1198356 TRANSCRIPTIONAL REGULATOR, RPIR FAMILY Gene name: RpiR NCBIProteinAccess:NP_541551.1 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17988918 NCBIGene: 1198345 LocusTag: BMEII0573 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YCF7 IOLE PROTEIN NCBIProteinAccess:NP_541548.1 Gene name: mocC This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Rhizopine/inositol catabolism [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YCG0 LocusTag: BMEII0570 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Rhizopine/inositol catabolism [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1198342 NCBIProteinGI: 17988915 exodeoxyribonuclease VII large subunit NCBIGene: 1198299 NCBIProteinAccess:NP_541505.1 NCBIProteinGI: 17988872 LocusTag: BMEII0527 PMID: 14638795 Gene name: xseA Molecule Role Annotation: FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. UniProtKB: PR:Q8YCK1 This protein is a Brucella virulence factor. FUNCTION: Bidirectionally degrades single-stranded DNA into large acid-insoluble oligonucleotides, which are then degraded further into small acid-soluble oligonucleotides (By similarity)(Swiss-Prot: Q8FVR1). CATALYTIC ACTIVITY: Exonucleolytic cleavage in either 5'- to 3'- or 3'- to 5'-direction to yield nucleoside 5'-phosphates(Swiss-Prot: Q8FVR1). SUBUNIT: Heterooligomer composed of large and small subunits (By similarity)(Swiss-Prot: Q8FVR1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8FVR1). SIMILARITY: Belongs to the xseA family(Swiss-Prot: Q8FVR1). MUTATION: xseA codes for an exodeoxyribonuclease. B. melitensis xseA mutant via signature-tagged mutagenesis is attenuated in vivo in mice [Ref6480:Lestrate et al., 2003]. glucose-6-phosphate 1-dehydrogenase UniProtKB: PR:Q8YCL5 Molecule Role Annotation: MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. NCBIGene: 1198285 PMID: 12761078 NCBIProteinAccess:NP_541491.1 Gene name: zwf LocusTag: BMEII0513 This protein is a Brucella virulence factor. MUTATION: Brucella abortus zwf mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells and macrophages [Ref6469:Kim et al., 2003]. NCBIProteinGI: 17988858 NICKEL-BINDING PERIPLASMIC PROTEIN PRECURSOR This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_541465.1 NCBIGene: 1198259 NCBIProteinGI: 17988832 PMID: 14979322 Gene name: nikA LocusTag: BMEII0487 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Ni2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages, Mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YCP1 D-GALACTARATE DEHYDRATASE PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988830 LocusTag: BMEII0485 UniProtKB: PR:Q8YCP3 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: D-galactarate dehydratase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: galcD NCBIProteinAccess:NP_541463.1 NCBIGene: 1198257 GntR family transcriptional regulator Gene name: gntR1 PMID: 16113274 NCBIGene: 1198247 NCBIProteinAccess:NP_541453 UniProtKB: PR:Q8YCQ3 Molecule Role Annotation: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIProteinGI: 17988820 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. LocusTag: BMEII0475 GenBank: AE008918 glycerol-3-phosphate dehydrogenase Molecule Role Annotation: MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6551:Burkhardt et al., 2005]. LocusTag: BMEII0429 NCBIProteinAccess:NP_541407.1 UniProtKB: PR:Q8YCU9 Gene name: eryB NCBIProteinGI: 17988774 This protein is a Brucella virulence factor. MUTATION: EryB is an erythritol phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. The B. suis eryB mutant by Tn5 transposon mutagenesis was attenuated in the human macrophage -like THP-1 cells. This mutant is sensitive to erythritol and mimics the erythritol sensitive response of the B19 strain [Ref6551:Burkhardt et al., 2005]. NCBIGene: 1198201 PMID: 10708387, 16177356 D-erythrulose 4-phosphate dehydrogenase NCBIProteinGI: 17988773 NCBIGene: 1198200 NCBIProteinAccess:NP_541406.1 PMID: 10708387, 16177356 Gene name: eryC Molecule Role Annotation: MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6551:Burkhardt et al., 2005]. UniProtKB: PR:Q8YCV0 LocusTag: BMEII0428 This protein is a Brucella virulence factor. MUTATION: The eryC gene encodes for enzyme Derythrulose-1-phosphate dehydrogenase. The vaccine strain B abortus B19 is the only known B abortus isolate whose growth is inhibited by erythritol. The B abortus B19 strain is an eryCD double mutant. The defect in B19 was complemented in trans by plasmids containing the complete ery region and by plasmids with Tn1725 insertions in eryA, eryB and eryD. Plasmids with Tn1725 insertions in eryC were the only ones that failed to complement the Ery phenotype of B19 [Ref6483:Sangari et al., 2000]. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50 to 90- fold reduced , but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALBc mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. In conclusion, erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B suis [Ref6551:Burkhardt et al., 2005]. TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY PMID: 16113274 NCBIGene: 1198162 UniProtKB: PR:Q8YCY7 Gene name: lysR12 Molecule Role Annotation: FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. LocusTag: BMEII0390 NCBIProteinAccess:NP_541368.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIProteinGI: 17988735 FORMATE DEHYDROGENASE ALPHA CHAIN PMID: 14979322 NCBIProteinGI: 17988723 Gene name: fdhA This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIGene: 1198150 LocusTag: BMEII0378 NCBIProteinAccess:NP_541356.1 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Formate dehydrogenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YCZ9 SUGAR TRANSPORT ATP-BINDING PROTEIN NCBIProteinAccess:NP_541339.1 NCBIGene: 1198133 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17988706 UniProtKB: PR:Q8YD16 Gene name: araG This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: L-arabinose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction, but not in Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0361 D-aminopeptidase Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_541328.1 NCBIGene: 1198122 NCBIProteinGI: 17988695 PMID: 14979322 Gene name: dacF This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Peptidoglycan synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YD27 LocusTag: BMEII0350 ABC TRANSPORTER PERMEASE PROTEIN NCBIProteinGI: 17988681 UniProtKB: PR:Q8YD41 PMID: 14979322 NCBIGene: 1198108 NCBIProteinAccess:NP_541314.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: BMEII0336 LocusTag: BMEII0336 6-AMINOHEXANOATE-DIMER HYDROLASE Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988663 LocusTag: BMEII0318 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: BMEII0318 NCBIProteinAccess:NP_541296.1 UniProtKB: PR:Q8YD59 NCBIGene: 1198090 LOW AFFINITY ZINC TRANSPORT MEMBRANE PROTEIN LocusTag: BMEII0308 UniProtKB: PR:Q8YD69 NCBIProteinGI: 17988653 Gene name: cobW NCBIProteinAccess:NP_541286.1 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1198080 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis cobW gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. PMID: 12438693 ribose ABC transporter ATP-binding protein Gene name: dbsA Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Ribose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988645 PMID: 14979322 NCBIProteinAccess:NP_541278 LocusTag: BMEII0300 UniProtKB: PR:Q8YD77 NCBIGene: 1198072 GenBank: AE008918 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Ribose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in HeLa [Ref6462:Delrue et al., 2004]. high-affinity zinc uptake system protein ZNUA NCBIProteinGI: 17988522 LocusTag: BMEII0178 Gene name: znuA NCBIGene: 1197949 Molecule Role Annotation: MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6550:Kim et al., 2004]. PMID: 12761078, 15472468 This protein is a Brucella virulence factor. MUTATION: Brucella abortus znuA mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B abortus, but contributes to utilization of zinc required for intracellular growth [Ref6550:Kim et al., 2004]. GenBank: AE008918 UniProtKB: PR:Q8YDJ7 NCBIProteinAccess:NP_541155 HIGH-AFFINITY ZINC UPTAKE SYSTEM ATP-BINDING PROTEIN ZNUC NCBIGene: 1197948 UniProtKB: PR:Q8YDJ8 LocusTag: BMEII0177 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: znuC NCBIProteinAccess:NP_541154.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Zn2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988521 PMID: 14979322 flagellar biosynthetic protein FlhA NCBIGene: 1197937 GenBank: AE008918 UniProtKB: PR:Q8YDK9 Gene name: flghA LocusTag: BMEII0166 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Export apparatus [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_541143 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Export apparatus [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988510 PMID: 14979322 flagellar hook protein FlgE UniProtKB: PR:Q8YDL6 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988503 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Hook [Ref6462:Delrue et al., 2004]. SIMILARITY: Belongs to the flagella basal body rod proteins family(Swiss-Prot: Q8FUS9). MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0159 NCBIProteinAccess:NP_541136.1 Gene name: flgE NCBIGene: 1197930 PMID: 14979322 two component response regulator Gene name: ftcR This protein is a Brucella virulence factor. MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria [Ref6549:Léonard et al., 2007]. UniProtKB: PR:Q8YDL7 PMID: 17056750 GenBank: NZ_GG703779 NCBIProteinGI: 17988502 NCBIProteinAccess:NP_541135 LocusTag: BMEII0158 Molecule Role Annotation: MUTATION: FtcR is required in B melitensis 16M for the transcription of the fliF gene during vegetative and intracellular growth, and for the production of the two structural flagellar components FlgE and FliC during vegetative growth. A ftcR mutant has the same virulence phenotype as previously found with structural flagellar mutants. In HeLa cells and bovine macrophages, no attenuation of the ftcR mutant was observed compared to the WT parental strain. In BALB/c mice, the ftcR mutant was not attenuated after 1 week of infection but was attenuated after 4 weeks of infection. FtcR acts as a flagellar master regulator in B melitensis and perhaps in other related alpha-proteobacteria [Ref6549:Léonard et al., 2007]. NCBIGene: 1197929 flagellar motor protein MotB PMID: 14979322 LocusTag: BMEII0154 Gene name: motB NCBIGene: 1197925 UniProtKB: PR:Q8YDM1 NCBIProteinAccess:NP_541131.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988498 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellar motor [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. FLAGELLAR M-RING PROTEIN FLIF This protein is a Brucella virulence factor. FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane Gene name: fliF PMID: multi-pass membrane protein (By similarity)(Swiss-Prot: Q8FUS3). SIMILARITY: Belongs to the fliF family(Swiss-Prot: Q8FUS3). MUTATION: fliF is a gene potentially coding for the MS ring, a basal component of the flagellar system. Its mutant through signature- tagged mutagenesis is attenuated in vivo. It implicate a role for flagella in virulenc [Ref6480:Lestrate et al., 2003]. NCBIGene: 1197922 NCBIProteinGI: 17988495 NCBIProteinAccess:NP_541128.1 Molecule Role Annotation: FUNCTION: The M ring may be actively involved in energy transduction (By similarity)(Swiss-Prot: Q8FUS3). SUBUNIT: The basal body constitutes a major portion of the flagellar organelle and consists of five rings (E,L,P,S, and M) mounted on a central rod. The M ring is integral to the inner membrane of the cell and may be connected to the flagellar rod via the S ring. The S (supramembrane ring) lies just distal to the M ring. The L and P rings lie in the outer membrane and the periplasmic space, respectively (By similarity)(Swiss-Prot: Q8FUS3). SUBCELLULAR LOCATION: Inner membrane LocusTag: BMEII0151 UniProtKB: PR:Q8YDM4 flagellin LocusTag: BMEII0150 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellin [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197921 PMID: 14979322 UniProtKB: PR:Q8YDM5 NCBIProteinAccess:NP_541127 GenBank: AE008918 Gene name: fliC NCBIProteinGI: 17988494 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Flagellin [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. homoprotocatechuate 2,3-dioxygenase UniProtKB: PR:Q8YDN9 NCBIGene: 1197907 Molecule Role Annotation: FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: Dioxygenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0136 NCBIProteinAccess:NP_541113 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: Dioxygenase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17988480 GenBank: AE008918 Gene name: pheB hypothetical protein This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Uncharacterised protein family (DUF0261) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: BMEII0128 PMID: 14979322 NCBIGene: 1197899 LocusTag: BMEII0128 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Uncharacterised protein family (DUF0261) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988472 NCBIProteinAccess:NP_541105.1 UniProtKB: PR:Q8YDP7 GntR family transcriptional regulator Molecule Role Annotation: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIProteinGI: 17988460 GenBank: GG703779 NCBIProteinAccess:NP_541093 Gene name: gntR10 UniProtKB: PR:Q8YDQ9 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. LocusTag: BMEII0116 NCBIGene: 1197887 PMID: 16113274 RIBOKINASE Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BMEII0089 Gene name: rbsK UniProtKB: PR:Q8YDT6 NCBIProteinGI: 17988433 NCBIGene: 1197860 NCBIProteinAccess:NP_541066.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribokinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. isochorismate synthase Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Sideophore sysnhesis, Fe3+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes [Ref6462:Delrue et al., 2004]. Gene name: dhbC NCBIGene: 1197848 PMID: 14979322 LocusTag: BMEII0077 NCBIProteinAccess:NP_541054 NCBIProteinGI: 17988421 UniProtKB: PR:Q8YDU7 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Sideophore sysnhesis, Fe3+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Pregant goat, but not in Mice, IFN-/-Mice, Macrophages, Trophoblastes [Ref6462:Delrue et al., 2004]. GenBank: AE008918 MG(2+) TRANSPORT ATPASE, P-TYPE PMID: 14979322 NCBIProteinAccess:NP_541033.1 NCBIGene: 1197827 Gene name: mgtB NCBIProteinGI: 17988400 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0056 Molecule Role Annotation: FUNCTIONAL GROUP: Metal acquisition [Ref6462:Delrue et al., 2004]. FUNCTION: Mg2+ uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YDW8 SENSORY TRANSDUCTION HISTIDINE KINASE Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEII0052 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIGene: 1197823 Gene name: nodV UniProtKB: PR:Q8YDX2 NCBIProteinGI: 17988396 NCBIProteinAccess:NP_541029.1 GLUTAMATE SYNTHASE [NADPH] LARGE CHAIN PMID: 10858227 LocusTag: BMEII0040 NCBIProteinGI: 17988384 Gene name: BMEII0040 NOT gltD This protein is a Brucella virulence factor. MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. NCBIProteinAccess:NP_541017.1 NCBIGene: 1197811 Molecule Role Annotation: MUTATION: gltD encodes the small subunit of glutamate synthase. It is required for B. abortus growth as shown in signature-tagged transposon mutagenesis. It suggests that glutamate may serve as carbon and/or nitrogen sources during growth of B abortus [Ref6463:Hong et al., 2000]. UniProtKB: PR:Q8YDY4 glutamate synthase subunit beta LocusTag: BMEII0039 NCBIGene: 1197810 PMID: 14979322 UniProtKB: PR:Q8YDY5 GenBank: AE008918 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Glut. sunthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 161511181 NCBIProteinAccess:NP_541016 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Glut. sunthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. Gene name: gltD ATPASE VIRB11 HOMOLOG LocusTag: BMEII0035 NCBIProteinGI: 17988379 NCBIProteinAccess:NP_541012.1 Gene name: virb11 This protein is a Brucella virulence factor. MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. PMID: 15312849 UniProtKB: PR:Q8YDY9 Molecule Role Annotation: MUTATION: The virB11 mutation experiment confirms that a complete VirB apparatus is required for their secretion [Ref6464:Marchesini et al., 2004]. NCBIGene: 1197806 channel protein VIRB10-like protein UniProtKB: PR:Q8YDZ0 Gene name: virb10 LocusTag: BMEII0034 NCBIProteinAccess:NP_541011 This protein is a Brucella virulence factor. MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6540:Sieira et al., 2000]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6547:Celli et al., 2003]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6463:Hong et al., 2000]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6538:Briones et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6548:Boschiroli et al., 2002]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. Molecule Role Annotation: MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6540:Sieira et al., 2000]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6547:Celli et al., 2003]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6463:Hong et al., 2000]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6538:Briones et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6548:Boschiroli et al., 2002]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. GenBank: AE008918 PMID: 10940027, 12925673, 10858227, 11401996, 12414154, 11260139 NCBIProteinGI: 17988378 NCBIGene: 1197805 CHANNEL PROTEIN VIRB9 HOMOLOG LocusTag: BMEII0033 UniProtKB: PR:Q8YDZ1 NCBIProteinAccess:NP_541010.1 NCBIProteinGI: 17988377 Molecule Role Annotation: MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6545:Rittig et al., 2001]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6546:Delrue et al., 2001]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. NCBIGene: 1197804 This protein is a Brucella virulence factor. MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6545:Rittig et al., 2001]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6546:Delrue et al., 2001]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. PMID: 11349069, 10510235, 11437834, 12414149 Gene name: virb9 CHANNEL PROTEIN VIRB6 HOMOLOG NCBIProteinGI: 17988374 NCBIProteinAccess:NP_541007.1 UniProtKB: PR:Q8YDZ2 NCBIGene: 1197801 Molecule Role Annotation: MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. Gene name: virb6 This protein is a Brucella virulence factor. MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. LocusTag: BMEII0030 VirB5 NCBIProteinAccess:NP_541006.1 This protein is a Brucella virulence factor. MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. NCBIGene: 1197800 Molecule Role Annotation: MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6543:Rouot et al., 2003]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6544:Porte et al., 2003]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6470:Sun et al., 2005]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. Gene name: virB5 UniProtKB: PR:Q8YDZ3 PMID: 12595417, 12595466, 16113325, 10510235 LocusTag: BMEII0029 NCBIProteinGI: 17988373 ATPASE VIRB4 HOMOLOG Gene name: virb4 Molecule Role Annotation: MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6541:Watarai et al., 2002]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6542:Kim et al., 2005]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. PMID: 11988518, 15869716, 15135535 LocusTag: BMEII0028 This protein is a Brucella virulence factor. MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6541:Watarai et al., 2002]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6542:Kim et al., 2005]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. NCBIProteinGI: 17988372 UniProtKB: PR:Q8YDZ4 NCBIProteinAccess:NP_541005.1 NCBIGene: 1197799 attachment mediating protein VIRB1-like protein This protein is a Brucella virulence factor. MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6539:den et al., 2004]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6540:Sieira et al., 2000]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. NCBIGene: 1197796 NCBIProteinAccess:NP_541002 GenBank: AE008918 LocusTag: BMEII0025 PMID: 15322008, 10940027, 16113325, 16272371 NCBIProteinGI: 17988369 Molecule Role Annotation: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6539:den et al., 2004]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6540:Sieira et al., 2000]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. Gene name: virb1 UniProtKB: PR:Q8YDZ5 imidazole glycerol phosphate synthase subunit HisF LocusTag: BMEI2041 Gene name: hisF NCBIGene: 1197752 UniProtKB: PR:Q8YE37 Molecule Role Annotation: FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 17988324 NCBIProteinAccess:NP_540958.1 PMID: L-histidine biosynthesis This protein is a Brucella virulence factor. FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The hisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the hisH subunit (By similarity)(Swiss-Prot: Q8FY07). CATALYTIC ACTIVITY: 5-[(5-phospho-1-deoxyribulos-1-ylamino)methylideneamino]-1-(5-phosphoribosyl)imidazole-4-carboxamide + L-glutamine = imidazole-glycerol phosphate + 5-aminoimidazol-4-carboxamide ribonucleotide + L-glutamate + H(2)O(Swiss-Prot: Q8FY07). PATHWAY: Amino-acid biosynthesis TRANSCRIPTIONAL REGULATORY PROTEIN CHVI NCBIProteinAccess:NP_540953.1 Gene name: bvrR UniProtKB: PR:Q8YE42 PMID: 16077108, 12414153, 9826346, 11401996, 12414149, 12218183 NCBIProteinGI: 17988319 LocusTag: BMEI2036 This protein is a Brucella virulence factor. MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. NCBIGene: 1197747 Molecule Role Annotation: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. SENSOR PROTEIN CHVG UniProtKB: PR:Q8YE43 Gene name: bvrS NCBIProteinAccess:NP_540952.1 LocusTag: BMEI2035 This protein is a Brucella virulence factor. MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. Molecule Role Annotation: MUTATION: The two-component BvrSBvrR system is essential for Brucella abortus virulence. Disruption of BvrSBvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. The bvrS and bvrR mutants are avirulent in mice, show reduced invasiveness to epithelial cells and macrophages, and are incapable of inhibiting lysosome fusion and replicating intracellularly [Ref6535:Manterola et al., 2005]. Mutations in the bvrR or bvrS genes hamper the penetration of B abortus in non-phagocytic cells and impairs intracellular trafficking and virulence. BvrRBvrS mutants do not recruit small GTPases of the Rho subfamily required for actin polymerization and penetration to cells. Dysfunction of the BvrRBvrS system alters the outer membrane permeability, the expression of several group 3 outer membrane proteins and the pattern of lipid A acylation. Constructs of virulent B abortus chimeras containing heterologous LPS from the bvrS(-) mutant demonstrated an altered permeability to cationic peptides similar to that of the BvrRBvrS mutants. It is hypothesized that the Brucella BvrRBvrS is a system devoted to the homeostasis of the outer membrane and, therefore in the interface for cell invasion and mounting the required structures for intracellular parasitism [Ref6536:López-Goñi et al., 2002]. In contrast to S2308 and S19, bvrS and bvrR mutant strains poorly invade HeLa cells and are rapidly targeted to cathepsin D- containing compartments [Ref6537:Pizarro-Cerdá et al., 1998]. B abortus bvrS bvrR mutants display reduced invasiveness and virulence [Ref6538:Briones et al., 2001]. Brucella bvrS and bvrR null mutants are defective in several outer membrane proteins, mainly Omp3a (former Omp25) and Omp3b as well as in the structure of the LPS molecule, but the O chain seems to be intact [Ref6466:Gorvel and Moreno, 2002]. Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surface- targeted bactericidal peptides, it is proposed that BvrRBvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments [Ref6499:Guzman-Verri et al., 2002]. BvrR/BvrS mutants are avirulent in mice, show reduced invasiveness in cells, and are unable to inhibit lysosome fusion and to replicate intracellularly [Ref6499:Guzman-Verri et al., 2002]. PMID: 16077108, 12414153, 9826346, 11401996, 12414149, 12218183 NCBIProteinGI: 17988318 NCBIGene: 1197746 molecular chaperone DnaK NCBIProteinGI: 17988285 PMID: 11854256 UniProtKB: PR:Q8YE76 Gene name: dnaK NCBIProteinAccess:NP_540919.1 This protein is a Brucella virulence factor. FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2). INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2). SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2). MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. Molecule Role Annotation: FUNCTION: Acts as a chaperone (By similarity)(Swiss-Prot: Q8FXX2). INDUCTION: By stress conditions e.g. heat shock (By similarity)(Swiss-Prot: Q8FXX2). SIMILARITY: Belongs to the heat shock protein 70 family(Swiss-Prot: Q8FXX2). MUTATION: The heat shock protein DnaK is essential for intramacrophagic replication of Brucella suis. The replacement of the stress-inducible, native dnaK promoter of B suis by the promoter of the constitutively expressed bla gene resulted in temperature-independent synthesis of DnaK. In contrast to a dnaK null mutant, this strain grew at 37 degrees C, with a thermal cutoff at 39 degrees C However, the constitutive dnaK mutant, which showed high sensitivity to H(2)O(2)-mediated stress , failed to multiply in murine macrophage-like cells and was rapidly eliminated in a mouse model of infection, adding strong arguments that stress-mediated and heat shock promoter-dependent induction of dnaK is a crucial event in the intracellular replication of B suis [Ref6500:Köhler et al., 2002]. Mutation studies indicated that DnaK, but not DnaJ, was required for growth at 37 degrees C in vitro. Viability of the dnaK null mutant was also greatly affected at low pH. In infection experiments performed with both mutants at the reduced temperature of 30 degrees C, the dnaK mutant of B suis survived but failed to multiply within U937 cells, whereas the wild-type strain and the dnaJ mutant multiplied normally. Complementation of the dnaK mutant with the cloned dnaK gene restored growth at 37 degrees C, increased resistance to acid pH, and increased intracellular multiplication [Ref6500:Köhler et al., 2002]. LocusTag: BMEI2002 NCBIGene: 1197713 formamidopyrimidine-DNA glycosylase This protein is a Brucella virulence factor. FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6). SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6). SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6). SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6). MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1197657 NCBIProteinGI: 17988229 PMID: 14979322 UniProtKB: PR:Q8YED2 Molecule Role Annotation: FUNCTION: Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity)(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine(Swiss-Prot: Q8FXR6). CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate(Swiss-Prot: Q8FXR6). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8FXR6). SUBUNIT: Monomer (By similarity)(Swiss-Prot: Q8FXR6). SIMILARITY: Belongs to the FPG family(Swiss-Prot: Q8FXR6). SIMILARITY: Contains 1 FPG-type zinc finger(Swiss-Prot: Q8FXR6). MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540863.1 LocusTag: BMEI1946 Gene name: mutM 30S ribosomal protein S1 PMID: 10678941 UniProtKB: PR:Q8YEG3 NCBIProteinAccess:NP_540832.1 LocusTag: BMEI1915 This protein is a Brucella virulence factor. MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. NCBIProteinGI: 17988198 Gene name: rpsA NCBIGene: 1197626 Molecule Role Annotation: MUTATION: rpsA is a B. suis gene identified by signature-tagged mutagenesis [Ref6484:Foulongne et al., 2000]. TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY NCBIProteinGI: 17988196 Molecule Role Annotation: FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIGene: 1197624 Gene name: lysR13 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIProteinAccess:NP_540830.1 LocusTag: BMEI1913 PMID: 16113274 UniProtKB: PR:Q8YEG5 Molybdopterin biosynthesis enzyme NCBIProteinGI: 17988185 PMID: 14979322 NCBIProteinAccess:NP_540819.1 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1902 NCBIGene: 1197613 Gene name: BMEI1902 UniProtKB: PR:Q8YEH6 phosphoglucomutase LocusTag: BMEI1886 NCBIProteinAccess:NP_540803.1 Molecule Role Annotation: MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6534:Ko and Splitter, 2003]. Gene name: pgm This protein is a Brucella virulence factor. MUTATION: Brucella pgm encodes the phosphoglucomutase. The B. abortus pgm mutant (B2211) lacks the O antigen. However, the core region of the mutant LPS migrated in Tricine-PAGE electrophoresis in a position that was indistinguishable from that of the wild type core. Although the exponential intracellular replication of the pgm mutant was delayed by approximately 20 h with respect to that of the wild type, the high number of recoverable bacteria at 48 h postinfection indicates that mutant strain B2211 replicates inside HeLa host cells [Ref6486:Ugalde et al., 2000]. B abortus phosphoglucomutase (pgm) insertional mutants were attenuated in vivo but not in vitro [Ref6534:Ko and Splitter, 2003]. NCBIGene: 1197597 NCBIProteinGI: 17988169 UniProtKB: PR:Q8YEJ2 PMID: 10992476, 12525425 Hypothetical Cytosolic Protein NCBIProteinAccess:NP_540796.1 NCBIGene: 1197590 NCBIProteinGI: 17988162 Gene name: BMEI1879 LocusTag: BMEI1879 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Mesorhizobium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YEJ9 PMID: 14979322 INTEGRAL MEMBRANE PROTEIN LocusTag: BMEI1859 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Uncharacterised protein family 0005 [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Uncharacterised protein family 0005 [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinAccess:NP_540776.1 NCBIGene: 1197570 UniProtKB: PR:Q8YEL9 Gene name: BMEI1859 NCBIProteinGI: 17988142 thiol:disulfide interchange protein CYCY precursor Gene name: cysY GenBank: NZ_GG703778 UniProtKB: PR:Q8YEM9 LocusTag: BMEI1849 PMID: 14979322 NCBIProteinAccess:NP_540766 NCBIGene: 1197560 NCBIProteinGI: 17988132 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide oxidoreducate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide oxidoreducate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. dihydroxy-acid dehydratase UniProtKB: PR:Q8YEN0 PMID: L-isoleucine biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis NCBIGene: 1197559 NCBIProteinGI: 17988131 LocusTag: BMEI1848 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: 2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H(2)O(Swiss-Prot: Q8G353). COFACTOR: Binds 1 4Fe-4S cluster (Potential)(Swiss-Prot: Q8G353). PATHWAY: Amino-acid biosynthesis NCBIProteinAccess:NP_540765.1 Gene name: ilvD hypothetical protein Gene name: BMEI1844 NCBIProteinGI: 17988127 NCBIGene: 1197555 UniProtKB: PR:Q8YEN4 LocusTag: BMEI1844 NCBIProteinAccess:NP_540761.1 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Domain of Unkown Function (DUF930) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Domain of Unkown Function (DUF930) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 CELLOBIOSE-PHOSPHORYLASE NCBIProteinAccess:NP_540754.1 NCBIProteinGI: 17988120 UniProtKB: PR:Q8YEP1 Gene name: ndvB This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BMEI1837 NCBIGene: 1197548 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Synthesis of cyclic ( [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, HeLa [Ref6462:Delrue et al., 2004]. PROTEIN YBIS PRECURSOR NCBIGene: 1197520 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: ERFK/YBIS/YCFS/YNHG family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540726.1 NCBIProteinGI: 17988092 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: ERFK/YBIS/YCFS/YNHG family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: BMEI1809 UniProtKB: PR:Q8YER8 PMID: 14979322 LocusTag: BMEI1809 PII uridylyl-transferase LocusTag: BMEI1804 This protein is a Brucella virulence factor. FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312). CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312). SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312). MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. Gene name: glnD Molecule Role Annotation: FUNCTION: Modifies, by uridylylation or deuridylylation the PII (glnB) regulatory protein (By similarity)(Swiss-Prot: Q8G312). CATALYTIC ACTIVITY: UTP + [protein-PII] = diphosphate + uridylyl-[protein-PII](Swiss-Prot: Q8G312). SIMILARITY: Belongs to the glnD family(Swiss-Prot: Q8G312). MUTATION: glnD encodes for a uridylyl transferase which is the primary sensor of nitrogen. The glnD mutant via signature-tagged transposon mutagenesis is attenuated in THP1 macrophages and HeLa cells. It supports the hypothesis that the concentration of glutamine in host cells is critical for the intracellular survival of Brucella [Ref6484:Foulongne et al., 2000]. NCBIProteinAccess:NP_540721.1 NCBIGene: 1197515 UniProtKB: PR:Q8YES3 NCBIProteinGI: 17988087 PMID: 10678941 nitrogen regulatory IIA protein Gene name: glnL NCBIGene: 1197497 GenBank: NZ_GG703778 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Nitrogen regulatory IIA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Nitrogen regulatory IIA [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988069 LocusTag: BMEI1786 UniProtKB: PR:Q8YEU1 PMID: 14979322 NCBIProteinAccess:NP_540703 SULFITE REDUCTASE (FERREDOXIN) PMID: 14979322 NCBIProteinGI: 17988049 Gene name: cysI UniProtKB: PR:Q8YEW1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Sulfite reductate [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1766 NCBIGene: 1197477 NCBIProteinAccess:NP_540683.1 B12-dependent methionine synthase NCBIGene: 1197470 LocusTag: BMEI1759 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540676.1 NCBIProteinGI: 17988042 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Met. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: metH UniProtKB: PR:Q8YEW8 ABC TRANSPORTER ATP-BINDING PROTEIN NCBIProteinAccess:NP_540659.1 LocusTag: BMEI1742 NCBIGene: 1197453 Gene name: exsA (not ortho to BRUSU exsA) Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17988025 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YEY5 MALTOSE/MALTODEXTRIN TRANSPORT ATP-BINDING PROTEIN MALK LocusTag: BMEI1713 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. Gene name: malK NCBIGene: 1197424 NCBIProteinGI: 17987996 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Maltose transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, but not in HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8YF14 NCBIProteinAccess:NP_540630.1 histidinol dehydrogenase PMID: L-histidine biosynthesis This protein is a Brucella virulence factor. FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis UniProtKB: PR:Q8YF59 NCBIProteinGI: 17987951 NCBIGene: 1197379 Gene name: hisD Molecule Role Annotation: FUNCTION: Catalyzes the sequential NAD-dependent oxidations of L-histidinol to L-histidinaldehyde and then to L-histidine (By similarity)(Swiss-Prot: Q8G2R2). CATALYTIC ACTIVITY: L-histidinol + 2 NAD(+) = L-histidine + 2 NADH(Swiss-Prot: Q8G2R2). COFACTOR: Binds 1 zinc ion per subunit (By similarity)(Swiss-Prot: Q8G2R2). PATHWAY: Amino-acid biosynthesis NCBIProteinAccess:NP_540585.1 LocusTag: BMEI1668 hypothetical protein PMID: 14979322 Gene name: BMEI1658 NCBIProteinAccess:NP_540575.1 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987941 NCBIGene: 1197369 LocusTag: BMEI1658 UniProtKB: PR:Q8YF67 glucose-6-phosphate isomerase UniProtKB: PR:Q8YF86 NCBIProteinAccess:NP_540553.1 NCBIProteinGI: 17987919 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation PMID: glycolysis LocusTag: BMEI1636 Molecule Role Annotation: CATALYTIC ACTIVITY: D-glucose 6-phosphate = D-fructose 6-phosphate(Swiss-Prot: Q8G2N3). PATHWAY: Carbohydrate degradation NCBIGene: 1197347 Gene name: pgi dihydroorotate dehydrogenase 2 PMID: 12761078 Molecule Role Annotation: MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. LocusTag: BMEI1611 Gene name: pyrD This protein is a Brucella virulence factor. MUTATION: B. suis pyrD mutation study indicated that pyrimidine synthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. NCBIProteinAccess:NP_540528.1 NCBIProteinGI: 17987894 UniProtKB: PR:Q8YFB1 NCBIGene: 1197322 SENSORY TRANSDUCTION HISTIDINE KINASE Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540523.1 LocusTag: BMEI1606 NCBIProteinGI: 17987889 NCBIGene: 1197317 UniProtKB: PR:Q8YFB6 Gene name: vsrB TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY NCBIGene: 1197284 Molecule Role Annotation: FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. Gene name: lysR18 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: lysR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIProteinAccess:NP_540490.1 LocusTag: BMEI1573 NCBIProteinGI: 17987856 UniProtKB: PR:Q8YFE9 PMID: 16113274 transport protein LocusTag: BMEI1553 NCBIProteinAccess:NP_540470.1 NCBIProteinGI: 17987836 Gene name: bacA UniProtKB: PR:Q8YFG9 PMID: 10741969, 12270820 Molecule Role Annotation: MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6533:Ferguson et al., 2002]. NCBIGene: 1197264 This protein is a Brucella virulence factor. MUTATION: B abortus bacA mutant exhibited decreased survival in macrophages and greatly accelerated clearance from experimentally infected mice compared to the virulent parental strain [Ref6487:LeVier et al., 2000]. R meliloti bacA gene encodes a putative cytoplasmic membrane transport protein required for symbiosis [Ref6487:LeVier et al., 2000]. The BacA protein is essential for the long-term survival of Sinorhizobium meliloti and Brucella abortus within acidic compartments in plant and animal cells , respectively. Mutation study showed that B. abortus BacA affects the distribution of LPS fatty acids, including a very-long-chain fatty acid thought to be unique to the alpha-proteobacteria[Ref6533:Ferguson et al., 2002]. TETRATRICOPEPTIDE REPEAT FAMILY PROTEIN NCBIGene: 1197242 Gene name: BMEI1531 NCBIProteinAccess:NP_540448.1 Molecule Role Annotation: FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: protein-protein interaction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1531 UniProtKB: PR:Q8YFI9 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Other genes [Ref6462:Delrue et al., 2004]. FUNCTION: protein-protein interaction [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987814 PMID: 14979322 phosphoribosylamine--glycine ligase PMID: IMP biosynthesis LocusTag: BMEI1519 NCBIProteinAccess:NP_540436.1 NCBIGene: 1197230 Gene name: purD UniProtKB: PR:Q8YFK1 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis NCBIProteinGI: 17987802 Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + 5-phospho-D-ribosylamine + glycine = ADP + phosphate + N(1)-(5-phospho-D-ribosyl)glycinamide(Swiss-Prot: Q8G2B1). PATHWAY: Nucleotide biosynthesis 1-deoxy-D-xylulose-5-phosphate synthase NCBIProteinAccess:NP_540415 UniProtKB: PR:Q8YFM2 Gene name: dxps PMID: 14979322 NCBIGene: 1197209 Molecule Role Annotation: FUNCTIONAL GROUP: Vitamines cofactors [Ref6462:Delrue et al., 2004]. FUNCTION: Thiamine synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Vitamines cofactors [Ref6462:Delrue et al., 2004]. FUNCTION: Thiamine synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. GenBank: NZ_GG703778 LocusTag: BMEI1498 NCBIProteinGI: 17987781 amidophosphoribosyltransferase UniProtKB: PR:Q8YFN2 LocusTag: BMEI1488 Molecule Role Annotation: MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. NCBIProteinGI: 17987771 NCBIProteinAccess:NP_540405.1 NCBIGene: 1197199 Gene name: purF PMID: 12761078 This protein is a Brucella virulence factor. MUTATION: A B. suis purF mutation experiment suggests that the purine biosynthesis pathway contributes to intracellular growth [Ref6469:Kim et al., 2003]. TLDD PROTEIN Gene name: tldD LocusTag: BMEI1468 UniProtKB: PR:Q8YFQ2 NCBIGene: 1197179 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Putative modulator of DNA gyrase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17987751 NCBIProteinAccess:NP_540385.1 threonine synthase Gene name: thrC LocusTag: BMEI1450 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1197161 UniProtKB: PR:Q8YFS0 NCBIProteinGI: 17987733 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Thre. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540367.1 C-DI-GMP PHOSPHODIESTERASE A-RELATED PROTEIN NCBIGene: 1197159 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: EAL domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YFS2 NCBIProteinGI: 17987731 NCBIProteinAccess:NP_540365.1 PMID: 14979322 LocusTag: BMEI1448 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: EAL domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: BMEI1448 2-HALOALKANOIC ACID DEHALOGENASE I This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: BMEI1443 NCBIProteinAccess:NP_540360.1 UniProtKB: PR:Q8YFS7 NCBIProteinGI: 17987726 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: haloacid dehalogenase-like hydrolase domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197154 LocusTag: BMEI1443 THIOL:DISULFIDE INTERCHANGE PROTEIN DSBA NCBIProteinGI: 17987723 NCBIProteinAccess:NP_540357.1 LocusTag: BMEI1440 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1197151 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: dsbA UniProtKB: PR:Q8YFT0 PMID: 14979322 PUTATIVE UNDECAPRENYL-PHOSPHATE ALPHA-N-ACETYLGLUCOSAMINYLTRANSFERASE Gene name: wbpL This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YFU4 NCBIGene: 1197137 NCBIProteinAccess:NP_540343.1 PMID: 14979322 NCBIProteinGI: 17987709 LocusTag: BMEI1426 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. PEROSAMINE SYNTHETASE LocusTag: BMEI1414 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Gene name: perA This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540331.1 UniProtKB: PR:Q8YFV3 NCBIGene: 1197125 NCBIProteinGI: 17987697 PMID: 14979322 MANNOSYLTRANSFERASE Gene name: wbkA NCBIGene: 1197115 NCBIProteinAccess:NP_540321.1 LocusTag: BMEI1404 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987687 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YFV9 PHOSPHOMANNOMUTASE NCBIGene: 1197107 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17987679 UniProtKB: PR:Q8YFW6 NCBIProteinAccess:NP_540313.1 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1396 Gene name: pmm MANNOSYLTRANSFERASE C NCBIGene: 1197104 NCBIProteinGI: 17987676 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1393 PMID: 14979322 NCBIProteinAccess:NP_540310.1 Gene name: wbpZ UniProtKB: PR:Q8YFW9 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. Hypothetical Cytosolic Protein NCBIGene: 1197072 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. Gene name: BMEI1361 NCBIProteinAccess:NP_540278.1 LocusTag: BMEI1361 NCBIProteinGI: 17987644 UniProtKB: PR:Q8YG01 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. PMID: 14979322 hypothetical protein NCBIProteinAccess:NP_540256.1 NCBIGene: 1197050 LocusTag: BMEI1339 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Agrobacterium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987622 UniProtKB: PR:Q8YG23 Gene name: BMEI1339 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella/Agrobacterium orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. SENSOR PROTEIN PHOQ Gene name: feuQ UniProtKB: PR:Q8YG26 NCBIProteinGI: 17987619 PMID: 14979322 NCBIProteinAccess:NP_540253.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: Histidine kinase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1336 NCBIGene: 1197047 PROTEASE DO NCBIProteinGI: 17987613 LocusTag: BMEI1330 Gene name: htrA This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002]. FUNCTION: Protease [Ref412:Kohler et al., 2002]. MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. UniProtKB: PR:Q8YG32 NCBIProteinAccess:NP_540247.1 Molecule Role Annotation: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref412:Kohler et al., 2002]. FUNCTION: Protease [Ref412:Kohler et al., 2002]. MUTATION: Attenuated in "Goat", Macrophages, but not in Mice [Ref412:Kohler et al., 2002]. NCBIGene: 1197041 PMID: 12438693 LPSA PROTEIN PMID: 14979322 Gene name: lpsA UniProtKB: PR:Q8YG36 NCBIGene: 1197037 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987609 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: putative glycosyltranferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540243.1 LocusTag: BMEI1326 GUANOSINE-3',5'-BIS(DIPHOSPHATE) 3'-PYROPHOSPHOHYDROLASE NCBIProteinGI: 17987579 LocusTag: BMEI1296 NCBIGene: 1197007 Molecule Role Annotation: FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: spotT UniProtKB: PR:Q8YG65 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: ppGpp synthetase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540213.1 dihydroorotase NCBIGene: 1196992 NCBIProteinAccess:NP_540198.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1281 NCBIProteinGI: 17987564 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: dihydroorotase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8YG80 Gene name: pyrC ABC TRANSPORTER ATP-BINDING PROTEIN This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. Gene name: BMEI1258 LocusTag: BMEI1258 NCBIGene: 1196969 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: ABC transporter [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinAccess:NP_540175.1 UniProtKB: PR:Q8YGA2 NCBIProteinGI: 17987541 phosphoribosylglycinamide formyltransferase PMID: 12761078 Molecule Role Annotation: MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. Gene name: purN LocusTag: BMEI1241 NCBIProteinGI: 17987524 NCBIGene: 1196952 NCBIProteinAccess:NP_540158.1 UniProtKB: PR:Q8YGB8 This protein is a Brucella virulence factor. MUTATION: B. abortus purN gene is essential for intracellular growth in HeLa cells as shown from transposon mutagenesis study [Ref6469:Kim et al., 2003]. phosphoribosylaminoimidazole synthetase NCBIProteinGI: 17987523 LocusTag: BMEI1240 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis NCBIGene: 1196951 NCBIProteinAccess:NP_540157.1 Gene name: purM PMID: IMP biosynthesis UniProtKB: PR:Q8YGB9 Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole(Swiss-Prot: Q8G1K5). PATHWAY: Nucleotide biosynthesis UDP-GLUCOSE 4-EPIMERASE LocusTag: BMEI1237 NCBIGene: 1196948 UniProtKB: PR:Q8YGC2 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinGI: 17987520 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: UDP-glucose 4-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: galE NCBIProteinAccess:NP_540154.1 Hypothetical exonuclease Gene name: BMEI1229 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Exonuclease X-T domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YGD0 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Exonuclease X-T domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1229 NCBIProteinGI: 17987512 NCBIGene: 1196940 NCBIProteinAccess:NP_540146.1 SERINE HYDROXYMETHYLTRANSFERASE Molecule Role Annotation: FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1196903 NCBIProteinAccess:NP_540109.1 PMID: 12438693 NCBIProteinGI: 17987475 This protein is a Brucella virulence factor. FUNCTION: Interconversion of serine and glycine(Swiss-Prot: Q8G1F1). CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine(Swiss-Prot: Q8G1F1). COFACTOR: Pyridoxal phosphate (By similarity)(Swiss-Prot: Q8G1F1). PATHWAY: Key enzyme in the biosynthesis of purines, lipids, hormones and other components(Swiss-Prot: Q8G1F1). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G1F1). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G1F1). SIMILARITY: Belongs to the SHMT family(Swiss-Prot: Q8G1F1). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glyA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. LocusTag: BMEI1192 Gene name: glyA UniProtKB: PR:Q8YGG7 phosphoribosylformylglycinamidine synthase II Gene name: purL NCBIProteinAccess:NP_540044.1 LocusTag: BMEI1127 PMID: IMP biosynthesis Molecule Role Annotation: CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183). PATHWAY: Nucleotide biosynthesis NCBIProteinGI: 17987410 UniProtKB: PR:Q8YGN1 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: ATP + N(2)-formyl-N(1)-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H(2)O = ADP + phosphate + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine + L-glutamate(Swiss-Prot: Q8G183). PATHWAY: Nucleotide biosynthesis NCBIGene: 1196838 ribulose-phosphate 3-epimerase NCBIGene: 1196827 GenBank: AE008917 UniProtKB: PR:Q8YGP2 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribulose-phosphate 3-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_540033 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Ribulose-phosphate 3-epimerase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: cbbE NCBIProteinGI: 17987399 LocusTag: BMEI1116 PMID: 14979322 ARGININE/ORNITHINE-BINDING PERIPLASMIC PROTEIN PRECURSOR LocusTag: BMEI1104 Gene name: artI Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987387 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Arginine transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 UniProtKB: PR:Q8YGQ4 NCBIGene: 1196815 NCBIProteinAccess:NP_540021.1 trigger factor This protein is a Brucella virulence factor. FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. Molecule Role Annotation: FUNCTION: Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation (By similarity)(Swiss-Prot: Q8G129). SIMILARITY: Belongs to the FKBP-type PPIase family. Tig subfamily(Swiss-Prot: Q8G129). SIMILARITY: Contains 1 PPIase FKBP-type domain(Swiss-Prot: Q8G129). MUTATION: tig encodes for Trigger factor that helps protein folding and secretion. It is one of the attenuated Signature-Tagged Mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice [Ref6480:Lestrate et al., 2003]. PMID: 14638795 Gene name: tig LocusTag: BMEI1069 NCBIProteinGI: 17987352 NCBIGene: 1196780 UniProtKB: PR:Q8YGT8 NCBIProteinAccess:NP_539986.1 OUTER MEMBRANE PROTEIN UniProtKB: PR:Q8YGU7 NCBIProteinGI: 17987343 NCBIGene: 1196771 LocusTag: BMEI1060 NCBIProteinAccess:NP_539977.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: dsbA PMID: 14979322 N-acetylmuramoyl-L-alanine amidase Gene name: amiC NCBIProteinAccess:NP_539973 UniProtKB: PR:Q8YGV1 NCBIProteinGI: 17987339 PMID: 14979322 NCBIGene: 1196767 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1056 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, peptidoglycan [Ref6462:Delrue et al., 2004]. FUNCTION: Cell-wall hydrolysis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. GenBank: AE008917 NIFS PROTEIN Gene name: nifS UniProtKB: PR:Q8YGW2 PMID: 14979322 NCBIProteinAccess:NP_539960.1 NCBIProteinGI: 17987326 Molecule Role Annotation: FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004]. FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1196754 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Nitrogen metabolism [Ref6462:Delrue et al., 2004]. FUNCTION: nitrogenase cofactor synthesis protein nifS [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BMEI1043 ABC TRANSPORTER ATP-BINDING PROTEIN NCBIProteinAccess:NP_539957.1 LocusTag: BMEI1040 PMID: 14979322 NCBIGene: 1196751 NCBIProteinGI: 17987323 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: dsbA UniProtKB: PR:Q8YGW5 molybdenum cofactor biosynthesis protein A NCBIGene: 1196730 UniProtKB: PR:Q8YGY6 NCBIProteinGI: 17987302 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539936.1 LocusTag: BMEI1019 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 Gene name: moaA NOT caiB MANNOSYLTRANSFERASE LocusTag: BMEI0997 NCBIProteinGI: 17987280 UniProtKB: PR:Q8YH07 Gene name: wbdA NCBIProteinAccess:NP_539914.1 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIGene: 1196708 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: O-chain biosynthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. GLUTAMINE SYNTHETASE NCBIProteinAccess:NP_539896.1 LocusTag: BMEI0979 NCBIGene: 1196690 NCBIProteinGI: 17987262 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. PMID: 12438693 Gene name: glnA UniProtKB: PR:Q8YH25 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis glnA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. cysteine synthase A NCBIProteinAccess:NP_539850.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Cys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: cysK UniProtKB: PR:Q8YH71 LocusTag: BMEI0933 PMID: 14979322 NCBIProteinGI: 17987216 NCBIGene: 1196644 Predicted acyl-CoA transferase/carnitine dehydratase NCBIProteinAccess:NP_539815.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17987181 UniProtKB: PR:Q8YHA4 Gene name: caiB Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: CAIB/BAIF family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BMEI0898 PMID: 14979322 NCBIGene: 1196609 TRANSCRIPTIONAL REGULATOR, GNTR FAMILY PMID: 16113274 Molecule Role Annotation: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. UniProtKB: PR:Q8YHC1 NCBIProteinGI: 17987164 Gene name: gntR5 NCBIGene: 1196592 LocusTag: BMEI0881 NCBIProteinAccess:NP_539798.1 excinuclease ABC subunit A LocusTag: BMEI0878 NCBIProteinAccess:NP_539795.1 Molecule Role Annotation: FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. This protein is a Brucella virulence factor. FUNCTION: The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 uvrA and 2 uvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by uvrB, the uvrA molecules dissociate (By similarity)(Swiss-Prot: Q8G0I9). SUBUNIT: Forms a heterotetramer with uvrB during the search for lesions (By similarity)(Swiss-Prot: Q8G0I9). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I9). SIMILARITY: Belongs to the ABC transporter family. UvrA subfamily(Swiss-Prot: Q8G0I9). SIMILARITY: Contains 2 ABC transporter domains(Swiss-Prot: Q8G0I9). MUTATION: B. abortus urvA and recA mutants exhibited greater sensitivity than the wild-type strain. Mutant strains carrying inactivated uvrA genes are typically less sensitive than recA mutants because there is only the loss of the nucleotide excision repair system, just one subset of the larger repair networks. However, it was found that the recA mutant conferred only a modest sensitivity to UV, substantially less sensitive than the uvrA mutant. High basal recA expression was observed in the uvrA repair mutant. The B abortus recA mutant exhibited a nearly fourfold decline in survival to murine peritoneal macrophages but nominal sensitivity for the uvrA and radA repair mutants [Ref6493:Roux et al., 2006]. PMID: 16816190 NCBIProteinGI: 17987161 Gene name: uvrA UniProtKB: PR:Q8YHC4 NCBIGene: 1196589 ATP-DEPENDENT PROTEASE LA Gene name: lon UniProtKB: PR:Q8YHC6 NCBIGene: 1196587 This protein is a Brucella virulence factor. FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7). CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7). SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7). SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7). MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. NCBIProteinGI: 17987159 PMID: 10672180 LocusTag: BMEI0876 Molecule Role Annotation: FUNCTION: Degrades short-lived regulatory and abnormal proteins in presence of ATP. Hydrolyzes two ATPs for each peptide bond cleaved in the protein substrate (By similarity)(Swiss-Prot: Q8G0I7). CATALYTIC ACTIVITY: Hydrolysis of proteins in presence of ATP(Swiss-Prot: Q8G0I7). SUBUNIT: Homotetramer (By similarity)(Swiss-Prot: Q8G0I7). SUBCELLULAR LOCATION: Cytoplasm (By similarity)(Swiss-Prot: Q8G0I7). SIMILARITY: Belongs to the peptidase S16 family(Swiss-Prot: Q8G0I7). SIMILARITY: Contains 1 Lon domain(Swiss-Prot: Q8G0I7). MUTATION: In contrast to the parent strain, the Brucella abortus lon mutant, was impaired in its capacity to form isolated colonies on solid medium at 41 degrees C and displayed an increased sensitivity to killing by puromycin and H2O2. Brucella abortus Lon homologue functions as a stress response protease that is required for wild-type virulence during the initial stages of infection in the mouse model, but is not essential for the establishment and maintenance of chronic infection in this host [Ref6494:Robertson et al., 2000]. Both single lon or clpA mutations had comparable effects on growth inhibition, suggesting that the concerned proteases Lon and ClpAP both degrade a number of specific proteins, but are also both involved in general degradation of abnormal proteins. Compared to the single mutants, the double mutant lon clpA was highly sensitive to canavanine. One possible explanation for this observation is that both proteases can substitute for each other to a large extent during bacterial growth. Hence, simultaneous inactivation or decrease in activation of both proteases, either by direct mutation or by elimination of the regulatory component ClpA, strongly increased growth inhibition [Ref6494:Robertson et al., 2000]. NCBIProteinAccess:NP_539793.1 NITROGEN REGULATION PROTEIN NTRY NCBIProteinAccess:NP_539784.1 NCBIGene: 1196578 This protein is a Brucella virulence factor. MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. Molecule Role Annotation: MUTATION: The NtrY protein is a sensor of an ntr-related regulon which may be part of the glnALG operon. This mutant has a weakly attenuated phenotype (reduction of 1.2 log units versus the wild type at 48 h postinfection) which could be explained by a pleiotropic effect on the ntr regulon, since the ntrC mutant did not show such a phenotype [Ref6484:Foulongne et al., 2000]. Gene name: ntrY LocusTag: BMEI0867 PMID: 10678941 UniProtKB: PR:Q8YHD4 NCBIProteinGI: 17987150 PEPTIDYL-PROLYL CIS-TRANS ISOMERASE D PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004]. FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539762.1 NCBIProteinGI: 17987128 NCBIGene: 1196556 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Stress proteins/Chaperones [Ref6462:Delrue et al., 2004]. FUNCTION: Rotamase D [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YHF6 LocusTag: BMEI0845 Gene name: ppiD UNDECAPRENYL PYROPHOSPHATE SYNTHETASE NCBIProteinGI: 17987110 Molecule Role Annotation: FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9). CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9). COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9). SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. NCBIGene: 1196538 This protein is a Brucella virulence factor. FUNCTION: Generates undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide (By similarity)(Swiss-Prot: Q8G0D9). CATALYTIC ACTIVITY: Di-trans,poly-cis-decaprenyl diphosphate + isopentenyl diphosphate = diphosphate + di-trans,poly-cis-undecaprenyl diphosphate(Swiss-Prot: Q8G0D9). COFACTOR: Magnesium (By similarity)(Swiss-Prot: Q8G0D9). SUBUNIT: Homodimer (By similarity)(Swiss-Prot: Q8G0D9). SIMILARITY: Belongs to the UPP synthetase family(Swiss-Prot: Q8G0D9). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis uppS gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. LocusTag: BMEI0827 UniProtKB: PR:Q8YHH3 Gene name: uppS PMID: 12438693 NCBIProteinAccess:NP_539744.1 DNA-directed RNA polymerase subunit alpha NCBIGene: 1196492 NCBIProteinGI: 17987064 NCBIProteinAccess:NP_539698.1 This protein is a Brucella virulence factor. FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. Molecule Role Annotation: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates(Swiss-Prot: Q8G094). CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)(Swiss-Prot: Q8G094). SUBUNIT: Homodimer. The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription (By similarity)(Swiss-Prot: Q8G094). DOMAIN: The N-terminal domain is essential for RNAP assembly and basal transcription, whereas the C-terminal domain is involved in interaction with transcriptional regulators and with upstream promoter elements (By similarity)(Swiss-Prot: Q8G094). SIMILARITY: Belongs to the RNA polymerase alpha chain family(Swiss-Prot: Q8G094). MUTATION: The rpoA gene codes for the essential alpha-subunit of the RNA polymerase. B. melitensis rpoA mutant was found by signature-tagged mutagenesis from a mouse infection model. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. RpoA is involved in virB regulation in vitro. The mutant (Tn5::rpoA) was more resistant to oxidative stress [Ref6480:Lestrate et al., 2003]. Gene name: rpoA PMID: 14638795 LocusTag: BMEI0781 UniProtKB: PR:Q8YHL6 LACTOYLGLUTATHIONE LYASE UniProtKB: PR:Q8YHR6 Gene name: gloA PMID: 14979322 NCBIProteinGI: 17987013 NCBIProteinAccess:NP_539647.1 LocusTag: BMEI0730 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIGene: 1196441 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Lactoylglutathione lyase (pyruvate metabolism) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. homoserine dehydrogenase UniProtKB: PR:Q8YHS1 GenBank: AE008917 Gene name: thrA Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Lys. synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539642 LocusTag: BMEI0725 PMID: 14979322 NCBIGene: 1196436 NCBIProteinGI: 17987008 cobyrinic acid a,c-diamide synthase PMID: 14638795 NCBIGene: 1196416 Gene name: cobB NCBIProteinGI: 17986988 LocusTag: BMEI0705 This protein is a Brucella virulence factor. FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020). PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020). SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020). MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. UniProtKB: PR:Q8YHU1 Molecule Role Annotation: FUNCTION: Responsible for the amidation of carboxylic groups at position A and C of either cobyrinic acid or hydrogenobrynic acid. NH(2) groups are provided by glutamine, and one molecule of ATP is hydrogenolyzed for each amidation (By similarity)(Swiss-Prot: Q8G020). PATHWAY: Cobalamin biosynthesis(Swiss-Prot: Q8G020). SIMILARITY: Belongs to the cobB/cobQ family. CobB subfamily(Swiss-Prot: Q8G020). MUTATION: 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M were screened in a mouse model of infection. 36 of them to be attenuated in vivo. cobB is one of them [Ref6480:Lestrate et al., 2003]. NCBIProteinAccess:NP_539622.1 INTEGRAL MEMBRANE PROTEIN / HEMOLYSIN NCBIGene: 1196382 Gene name: BMEI0671 NCBIProteinAccess:NP_539588.1 PMID: 14979322 UniProtKB: PR:Q8YHX5 NCBIProteinGI: 17986954 LocusTag: BMEI0671 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Terc dome (efflux) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Terc dome (efflux) [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. TRANSCRIPTIONAL REGULATOR, GNTR FAMILY / MULTIPLE SUBSTRATE AMINOTRANSFERASE UniProtKB: PR:Q8YI19 NCBIProteinAccess:NP_539543.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BMEI0626 NCBIGene: 1196337 Gene name: aspB Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Unkown [Ref6462:Delrue et al., 2004]. FUNCTION: Aminotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17986909 ketol-acid reductoisomerase NCBIProteinGI: 17986907 Molecule Role Annotation: CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). PATHWAY: Amino-acid biosynthesis NCBIProteinAccess:NP_539541.1 This protein is a Brucella virulence factor. CATALYTIC ACTIVITY: (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). CATALYTIC ACTIVITY: (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH(Swiss-Prot: Q8FZU1). PATHWAY: Amino-acid biosynthesis LocusTag: BMEI0624 NCBIGene: 1196335 PMID: L-isoleucine biosynthesis Gene name: ilvCv UniProtKB: PR:Q8YI21 acetolactate synthase 3 catalytic subunit This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Val. Leu., Isoleu. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. GenBank: HD006899 Gene name: ilvI Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Val. Leu., Isoleu. Synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YI28 NCBIGene: 1196328 PMID: 14979322 LocusTag: BMEI0617 NCBIProteinGI: 17986900 NCBIProteinAccess:NP_539534 tRNA delta(2)-isopentenylpyrophosphate transferase NCBIGene: 1196327 NCBIProteinGI: 17986899 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB: PR:Q8YI29 Gene name: miaA LocusTag: BMEI0616 PMID: 12438693 NCBIProteinAccess:NP_539533.1 Molecule Role Annotation: FUNCTION: Catalyzes the first step in the biosynthesis of 2-methylthio-N6-(delta(2)-isopentenyl)-adenosine (MS[2]I[6]A) adjacent to the anticodon of several tRNA species (By similarity)(Swiss-Prot: Q8CY40). CATALYTIC ACTIVITY: Isopentenyl diphosphate + tRNA = diphosphate + tRNA containing 6-isopentenyladenosine(Swiss-Prot: Q8CY40). SIMILARITY: Belongs to the IPP transferase family(Swiss-Prot: Q8CY40). MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis miaA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. PHOSPHOSERINE PHOSPHATASE UniProtKB: PR:Q8YI30 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis serB gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: serB PMID: 12438693 NCBIProteinAccess:NP_539532.1 NCBIProteinGI: 17986898 LocusTag: BMEI0615 NCBIGene: 1196326 bicyclomycin resistance protein Gene name: bicA LocusTag: BMEI0605 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YI40 NCBIProteinGI: 17986888 GenBank: AE008917 NCBIGene: 1196316 PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539522 INTEGRAL MEMBRANE PROTEIN UniProtKB: PR:Q8YIA0 PMID: 12761078, 15135535 NCBIProteinAccess:NP_539462.1 LocusTag: BMEI0545 Gene name: pncA NCBIGene: 1196256 Molecule Role Annotation: MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. This protein is a Brucella virulence factor. MUTATION: Brucella abortus pnc mutant via mini-Tn5Km2 transposon mutagenesis has intracellular growth defect inside HeLa cells [Ref6469:Kim et al., 2003]. Nicotinamidasepyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages [Ref6468:Kim et al., 2004]. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from mouse spleens after 10 weeks [Ref6468:Kim et al., 2004]. It indicates that the mutant has reduced virulence in mice. NCBIProteinGI: 17986828 carbamoyl phosphate synthase small subunit PMID: 14979322 NCBIGene: 1196237 UniProtKB: PR:Q8YIB8 GenBank: NZ_GG703780 LocusTag: BMEI0526 NCBIProteinGI: 161511156 Gene name: carAB NCBIProteinAccess:NP_539443 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Clut. and pyr. Syntheis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Clut. and pyr. Syntheis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. aspartate aminotransferase NCBIProteinAccess:NP_539433.1 NCBIGene: 1196227 Gene name: aspC NCBIProteinGI: 17986799 LocusTag: BMEI0516 UniProtKB: PR:Q8YIC8 Molecule Role Annotation: MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. PMID: 12761078 This protein is a Brucella virulence factor. MUTATION: aspC encodes for an aminotransferase. B.abortus aspC mutant obtained from randomized miniTn5Km2 transposon mutagenesis showed decreased intracellular survival inside HeLa cells. So B. abortus aspC gene is essential for HeLa cell intracellular growth [Ref6469:Kim et al., 2003]. TRANSCRIPTIONAL REGULATORY PROTEIN, LYSR FAMILY PMID: 14979322 NCBIProteinGI: 17986796 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: lysR This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539430.1 LocusTag: BMEI0513 NCBIGene: 1196224 UniProtKB: PR:Q8YID1 thioredoxin reductase LocusTag: BMEI0512 Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Thioredoxin reductase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. Gene name: trkH GenBank: NZ_GG703780 NCBIGene: 1196223 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Thioredoxin reductase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17986795 UniProtKB: PR:Q8YID2 NCBIProteinAccess:NP_539429 PMID: 14979322 LIPOPOLYSACCHARIDE CORE BIOSYNTHESIS MANNOSYLTRANSFERASE LPCC NCBIProteinGI: 17986792 NCBIProteinAccess:NP_539426.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: Core synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Envelope molecules, Lipopolysaccharide [Ref6462:Delrue et al., 2004]. FUNCTION: Core synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BMEI0509 Gene name: lpsB UniProtKB: PR:Q8YID5 NCBIGene: 1196220 GLUTATHIONE S-TRANSFERASE UniProtKB: PR:Q8YII9 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Glutathione S-transferase, C-terminal domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Glutathione S-transferase, C-terminal domain [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17986738 PMID: 14979322 NCBIProteinAccess:NP_539372.1 LocusTag: BMEI0455 NCBIGene: 1196166 Gene name: BMEI0455 2-isopropylmalate synthase PMID: L-leucine biosynthesis This protein is a Brucella virulence factor. FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis NCBIGene: 1196162 UniProtKB: PR:Q8YIJ3 LocusTag: BMEI0451 Gene name: leuA Molecule Role Annotation: FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate)(Swiss-Prot: Q8FZC4). CATALYTIC ACTIVITY: Acetyl-CoA + 3-methyl-2-oxobutanoate + H(2)O = (2S)-2-isopropylmalate + CoA(Swiss-Prot: Q8FZC4). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 17986734 NCBIProteinAccess:NP_539368.1 PERIPLASMIC DIPEPTIDE TRANSPORT PROTEIN PRECURSOR NCBIProteinAccess:NP_539350.1 PMID: 14979322 UniProtKB: PR:Q8YIL1 NCBIGene: 1196144 LocusTag: BMEI0433 Gene name: dppA Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17986716 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Dipeptide uptake [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. nodulation protein NOLR NCBIGene: 1196141 PMID: 16113274 GenBank: AE008917 LocusTag: BMEI0430 NCBIProteinGI: 17986713 UniProtKB: PR:Q8YIL4 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: ArsR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. Gene name: arsR6 NCBIProteinAccess:NP_539347 Molecule Role Annotation: FUNCTIONAL GROUP: ArsR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. DISULFIDE BOND FORMATION PROTEIN B NCBIGene: 1196095 Gene name: dsbB Molecule Role Annotation: FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YIQ9 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Oxidoreduction [Ref6462:Delrue et al., 2004]. FUNCTION: Disulfide bond formation protein [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages [Ref6462:Delrue et al., 2004]. LocusTag: BMEI0384 NCBIProteinAccess:NP_539301.1 PMID: 14979322 NCBIProteinGI: 17986667 DNA-3-METHYLADENINE GLYCOSIDASE NCBIProteinAccess:NP_539299.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI0382 NCBIGene: 1196093 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Repair [Ref6462:Delrue et al., 2004]. FUNCTION: HhH-GPD superfamily base excision DNA repair [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. UniProtKB: PR:Q8YIR1 Gene name: alkA NCBIProteinGI: 17986665 PMID: 14979322 periplasmic component of efflux system NCBIGene: 1196070 NCBIProteinAccess:NP_539276.1 Gene name: macA NCBIProteinGI: 17986642 UniProtKB: PR:Q8YIT3 LocusTag: BMEI0359 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Transpter [Ref6462:Delrue et al., 2004]. FUNCTION: Macrolide efflux [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 TRANSCRIPTIONAL REGULATORY PROTEIN, ASNC FAMILY UniProtKB: PR:Q8YIT5 NCBIProteinGI: 17986640 Gene name: ansC NCBIGene: 1196068 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI0357 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Transcriptional regulator [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 NCBIProteinAccess:NP_539274.1 GntR family transcriptional regulator This protein is a Brucella virulence factor. FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. LocusTag: BMEI0320 Molecule Role Annotation: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. UniProtKB: PR:Q8YIW9 NCBIProteinGI: 17986603 GenBank: AE008917 Gene name: gntR17 NCBIGene: 1196031 NCBIProteinAccess:NP_539237 PMID: 16113274 DeoR family transcriptional regulator PMID: 16113274 LocusTag: BMEI0305 NCBIGene: 1196016 NCBIProteinAccess:NP_539222 Molecule Role Annotation: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. NCBIProteinGI: 17986588 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated in mice [Ref6530:Haine et al., 2005]. GenBank: AE008917 UniProtKB: PR:Q8YIY4 Gene name: gntR2 ATP-dependent DNA helicase LocusTag: BMEI0275 NCBIProteinAccess:NP_539193 NCBIGene: 1195987 GenBank: AE008917 NCBIProteinGI: 17986559 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: RNA helicase family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. PMID: 14979322 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Regulation [Ref6462:Delrue et al., 2004]. FUNCTION: RNA helicase family [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: mgps UniProtKB: PR:Q8YJ11 MEMBRANE PROTEIN MOSC NCBIProteinGI: 17986551 PMID: 14979322 LocusTag: BMEI0267 NCBIProteinAccess:NP_539185.1 UniProtKB: PR:Q8YJ19 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Rhizopine transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIGene: 1195979 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Rhizopine transport [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Mice, but not in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. Gene name: mosC pyruvate carboxylase NCBIProteinGI: 17986550 This protein is a Brucella virulence factor. MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. NCBIGene: 1195978 UniProtKB: PR:Q8YJ20 NCBIProteinAccess:NP_539184.1 LocusTag: BMEI0266 PMID: 10678941 Gene name: pyc Molecule Role Annotation: MUTATION: pyc is one B. suis gene identified by signature-tagged mutagenesis. It is essential for survival and mulitplication in macrophages [Ref6484:Foulongne et al., 2000]. HIGH-AFFINITY BRANCHED-CHAIN AMINO ACID TRANSPORT SYSTEM PERMEASE PROTEIN LIVH UniProtKB: PR:Q8YJ28 Molecule Role Annotation: FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. Gene name: livH NCBIGene: 1195970 NCBIProteinGI: 17986542 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: a.a. metabolism, Transport [Ref6462:Delrue et al., 2004]. FUNCTION: Branched as transport system [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Differential fluorescence induction [Ref6462:Delrue et al., 2004]. PMID: 14979322 LocusTag: BMEI0258 NCBIProteinAccess:NP_539176.1 phosphoenolpyruvate-protein phosphotransferase PTSP NCBIGene: 1195902 GenBank: NZ_GG703778 Gene name: pstP UniProtKB: PR:Q8YJ96 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Phosphoenolypruvate phosphotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. LocusTag: BMEI0190 NCBIProteinGI: 17986474 NCBIProteinAccess:NP_539108 PMID: 14979322 Molecule Role Annotation: FUNCTIONAL GROUP: "Classical virulence factors", Secretion of transport system, Flagella [Ref6462:Delrue et al., 2004]. FUNCTION: Phosphoenolypruvate phosphotransferase [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. TRANSCRIPTIONAL REGULATOR, GNTR FAMILY / AMINOTRANSFERASE CLASS-I This protein is a Brucella virulence factor. FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. PMID: 16113274 LocusTag: BMEI0169 Molecule Role Annotation: FUNCTIONAL GROUP: gntR family [Ref6530:Haine et al., 2005]. MUTATION: Attenuated using plasmid-tagged mutagenesis method [Ref6530:Haine et al., 2005]. NCBIProteinGI: 17986453 NCBIGene: 1195881 NCBIProteinAccess:NP_539087.1 UniProtKB: PR:Q8YJB7 Gene name: gntR4 isopropylmalate isomerase large subunit Gene name: leuC NCBIProteinAccess:NP_539075.1 NCBIGene: 1195869 UniProtKB: PR:Q8YJC9 This protein is a Brucella virulence factor. FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis LocusTag: BMEI0157 Molecule Role Annotation: FUNCTION: Catalyzes the isomerization between 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2R,3S)-3-isopropylmalate = (2S)-2-isopropylmaleate + H(2)O(Swiss-Prot: Q8FYG9). CATALYTIC ACTIVITY: (2S)-2-isopropylmaleate + H(2)O = 3-hydroxy-4-methyl-3-carboxypentanoate(Swiss-Prot: Q8FYG9). COFACTOR: Binds 1 4Fe-4S cluster per subunit (By similarity)(Swiss-Prot: Q8FYG9). PATHWAY: Amino-acid biosynthesis NCBIProteinGI: 17986441 PMID: L-leucine biosynthesis hypothetical protein Gene name: BMEI0085 UniProtKB: PR:Q8YJJ8 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539003.1 LocusTag: BMEI0085 NCBIGene: 1195797 Molecule Role Annotation: FUNCTIONAL GROUP: Unkown function [Ref6462:Delrue et al., 2004]. FUNCTION: Brucella orphan gene [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages [Ref6462:Delrue et al., 2004]. NCBIProteinGI: 17986369 PMID: 14979322 DIAMINOPIMELATE DECARBOXYLASE NCBIProteinAccess:NP_539002.1 NCBIGene: 1195796 LocusTag: BMEI0084 NCBIProteinGI: 17986368 This protein is a Brucella virulence factor. MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. UniProtKB: PR:Q8YJJ9 PMID: 12438693 Molecule Role Annotation: MUTATION: A study with miniTn5 mutants of B. suis constitutively expressing gfp indicates that B. suis lysA gene is required for intracellular multiplication in human macrophage THP-1 cells [Ref412:Kohler et al., 2002]. Gene name: lysA hypoxanthine-guanine phosphoribosyltransferase NCBIGene: 1195794 NCBIProteinGI: 17986366 Gene name: hpt PMID: 14979322 LocusTag: BMEI0082 UniProtKB: PR:Q8YJK1 Molecule Role Annotation: FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. NCBIProteinAccess:NP_539000.1 This protein is a Brucella virulence factor. FUNCTIONAL GROUP: DNA/RNA metabolism, Synthesis [Ref6462:Delrue et al., 2004]. FUNCTION: Purines synthesis [Ref6462:Delrue et al., 2004]. MUTATION: Attenuated in Macrophages, HeLa [Ref6462:Delrue et al., 2004]. two component response regulator NCBIProteinGI: 17986350 Gene name: BMEI0066 Molecule Role Annotation: MUTATION: BMEI0066 deletion mutant fails to replicated in murine macrophages and is rapidly cleared from the spleens of experimentally infected BALB/c mice [Ref7314:Zhang et al., 2009]. LocusTag: BMEI0066 GenBank: NZ_GG703778 UniProtKB: PR:Q8YJL6 This protein is a Brucella virulence factor. MUTATION: BMEI0066 deletion mutant fails to replicated in murine macrophages and is rapidly cleared from the spleens of experimentally infected BALB/c mice [Ref7314:Zhang et al., 2009]. NCBIProteinAccess:NP_538984 NCBIGene: 1195778 PMID: 19742243 type IV secretion system protein VirB10 Molecule Role Annotation: MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6465:Comerci et al., 2001]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6465:Comerci et al., 2001]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6465:Comerci et al., 2001]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6465:Comerci et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6465:Comerci et al., 2001]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. GenBank: AE014292 NCBIProteinGI: 23499827 Gene name: virB10 NCBIProteinAccess:NP_699267 PMID: 11260139 This protein is a Brucella virulence factor. MUTATION: Mutants with polar and nonpolar mutations introduced in irB10 showed different behaviors in mice and in the HeLa cell infection assay, suggesting that virB10 per se is necessary for the correct function of this type IV secretion apparatus [Ref6465:Comerci et al., 2001]. A B. abortus virB10 mutant showed a decrease of intracellular live bacteria comparable to that of the wild-type strain until 4 h after infection, indicating that a functional VirB system is not required for the short-term survival of Brucella inside macrophages. At later time points, the number of live virB10 mutants progressively decreased. Hence, the Brucella virB10 strain did not replicate, but rather was killed. Although the virB10 mutants are capable of short-term survival, they can not evade long-term degradation through fusion with lysosomes [Ref6465:Comerci et al., 2001]. B abortus virB1 and virB10 mutants are unable to persist in mouse spleens after i.p. inoculation, suggest that attenuation in the animal model is due to an inability of these strains to grow intracellularly [Ref6465:Comerci et al., 2001]. A B abortus virB10 mutant lost the ability to multiply in HeLa cells and was not recovered from the spleens of infected BALBc mice [Ref6465:Comerci et al., 2001]. The non polar virB10 mutant was able to block the acquisition of cathepsin D, but was not able to translocate to the replication compartment [Ref6465:Comerci et al., 2001]. The virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but , diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface [Ref6465:Comerci et al., 2001]. UniProtKB: PR:Q9RPX5 LocusTag: BRA0060 NCBIGene: 1164497 type IV secretion system protein VirB9 NCBIGene: 1164498 NCBIProteinGI: 23499828 Molecule Role Annotation: MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6466:Gorvel and Moreno, 2002]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6466:Gorvel and Moreno, 2002]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. PMID: 12414149 This protein is a Brucella virulence factor. MUTATION: Uptake in the presence or absence of Ca2 and Mg2 did not influence the subsequent intracellular survival of wild-type Brucella, whereas the decrease in the number of surviving virB9 mutant cells was delayed in the absence of Ca2 and Mg2. Possibly two types of adhesion molecules promoted uptake of Brucella, one being Ca2 and Mg2 dependent and the other not, and that both types participate in the uptake of wild-type bacteria but only the latter type participates in the uptake of the virB9 mutant [Ref6466:Gorvel and Moreno, 2002]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6466:Gorvel and Moreno, 2002]. The intracellular fate of three virB mutants (virB2, virB4 and virB9) in HeLa cells by immunofluorescence was examined. The three VirB proteins are not necessary for penetration and the inhibition of phago-lysosomal fusion within non-professional phagocytes. Rather, the virB mutants are unable to reach the replicative niche and reside in a membrane -bound vacuole expressing the late endosomal marker, LAMP1, and the sec61beta protein from the ER membrane, proteins that are present in autophagic vesicles originating from the ER [Ref6466:Gorvel and Moreno, 2002]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1 -positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. Gene name: virB9 NCBIProteinAccess:NP_699268.1 UniProtKB: PR:Q9RPX6 LocusTag: BRA0061 VirB8 Gene name: virB8 LocusTag: BMEII0032 This protein is a Brucella virulence factor. MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. NCBIProteinAccess:NP_541009.1 Molecule Role Annotation: MUTATION: virB8 mutant was attenuated by a mini-Tn5 transposon mutagenesis [Ref6484:Foulongne et al., 2000]. Attenuated non-polar virB2, virB4, virB8, virB9 and virB10 Brucella mutants are capable of penetrating cells as the same rate as the virulent wild-type Brucella, transit through EEA1-positive early compartments and then localize in LAMP1-positive compartments at early times of infection [Ref6466:Gorvel and Moreno, 2002]. NCBIGene: 1197803 PMID: 10678941, 12414149 NCBIProteinGI: 17988376 UniProtKB: PR:Q9RPX7 type IV secretion system protein VirB6 LocusTag: BRA0064 NCBIProteinAccess:NP_699271.1 NCBIProteinGI: 23499831 This protein is a Brucella virulence factor. MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. UniProtKB: PR:Q9RPX9 Gene name: virB6 NCBIGene: 1164501 Molecule Role Annotation: MUTATION: B. abortus virB6 is essential for intracellular growth within HeLa cells as shown from a mutagenesis study. type IV secretion system protein VirB5 NCBIGene: 1164502 UniProtKB: PR:Q9RPY0 LocusTag: BRA0065 NCBIProteinAccess:NP_699272.1 Molecule Role Annotation: MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6467:O'Callaghan et al., 1999]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6467:O'Callaghan et al., 1999]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6467:O'Callaghan et al., 1999]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. PMID: 10510235 NCBIProteinGI: 23499832 This protein is a Brucella virulence factor. MUTATION: A comparison of the VirB8 and VirB5 contents after induction of the B suis wild type and of virB5 and virB12 mutants further confirmed that the virB5 and virB12 genes belong to the same operon [Ref6467:O'Callaghan et al., 1999]. Smooth strains of Brucella unable to replicate (ie, killed B suis or the avirulent mutant B suis virB5) exhibit delayed phagosome-lysosome fusion [Ref6467:O'Callaghan et al., 1999]. Polar mutations in the operon upstream of virB5 exert a greater effect on the expression of virB5 than they do on the expression of the downstream gene virB12. It indicates that in B abortus , regulatory elements other than the virB promoter may influence VirB12 protein levels [Ref6467:O'Callaghan et al., 1999]. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages [Ref6467:O'Callaghan et al., 1999]. Gene name: virB5 type IV secretion system protein VirB4 NCBIProteinAccess:NP_699273.1 LocusTag: BRA0066 NCBIProteinGI: 23499833 UniProtKB: PR:Q9RPY1 This protein is a Brucella virulence factor. MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6468:Kim et al., 2004]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6468:Kim et al., 2004]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. PMID: 15135535 NCBIGene: 1164503 Molecule Role Annotation: MUTATION: A mutant strain of B abortus that contains an in-frame deletion in virB4 is unable to replicate in macrophages and survives in mice [Ref6468:Kim et al., 2004]. ntracellular replication was inhibited in wild-type B abortus after introducing a plasmid expressing a mutant VirB4 altered in the NTP -binding region. VirB4 containing the intact NTP -binding region is essential for evasion of fusion with lysosomes (11988518). The ruffling associated with internalization of the virB4 mutant results in a more rapid uptake than for the wild-type strain. The virB4 mutant shows primarily small regions of phalloidin staining at the sites of binding. Macrophages incubated simultaneously with B abortus and the fluid-phase marker tetramethyl rhodamine isothiocyanate (TRITC)-dextran accumulate the marker in large vacuoles containing the wild-type strain, but little or no marker accumulates in phagosomes containing the virB4 mutant. Similarly, phase-contrast micrographs have shown the wild-type strain in large phase-transparent compartments, but the virB4 mutant is in much smaller compartments (14738898). Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion [Ref6468:Kim et al., 2004]. The B abortus virB4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Splenomegaly was not observed at all in mice infected with virB4 mutant [Ref6468:Kim et al., 2004]. Gene name: virB4 VirB3 Molecule Role Annotation: MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. Gene name: virB3 This protein is a Brucella virulence factor. MUTATION: The B abortus virB3 gene is found to be essential for intracellular growth inside HeLa cells [Ref6469:Kim et al., 2003]. NCBIProteinAccess:NP_541004.1 PMID: 12761078 LocusTag: BMEII0027 NCBIGene: 1197798 NCBIProteinGI: 17988371 UniProtKB: PR:Q9RPY2 VirB2 PMID: 15322008, 16113325 UniProtKB: PR:Q9RPY3 NCBIGene: 1197797 Gene name: virB2 This protein is a Brucella virulence factor. MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. Molecule Role Annotation: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB2 mutant was unable to cause persistent infection in the mouse model, demonstrating the essential role of VirB2 in the function of the T4SS apparatus during infection [Ref6539:den et al., 2004]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6470:Sun et al., 2005]. NCBIProteinAccess:NP_541003.1 LocusTag: BMEII0026 NCBIProteinGI: 17988370 type IV secretion system protein VirB1 NCBIGene: 1164506 UniProtKB: PR:Q9RPY4 LocusTag: BRA0069 Gene name: virB1 PMID: 16272371 This protein is a Brucella virulence factor. MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6471:Höppner et al., 2005]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6471:Höppner et al., 2005]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6471:Höppner et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. NCBIProteinGI: 23499836 NCBIProteinAccess:NP_699276 Molecule Role Annotation: MUTATION: The Brucella abortus virB operon, encoding a type IV secretion system (T4SS), is required for intracellular replication and persistent infection in the mouse model. The products of the first two genes of the virB operon, virB1 and virB2, are predicted to be localized at the bacterial surface. Both mutants were shown to be nonpolar, as demonstrated by their ability to express the downstream gene virB5 during stationary phase of growth in vitro. Both VirB1 and VirB2 were essential for intracellular replication in J774 macrophages. The nonpolar virB1 mutant persisted at wild-type levels, showing that the function of VirB1 is dispensable in the mouse model of persistent infection [Ref6471:Höppner et al., 2005]. A B abortus polar virB1 mutant failed to replicate in HeLa cells, indicating that the virB operon plays a critical role in intracellular multiplication [Ref6471:Höppner et al., 2005]. Polar mutations in the virB1 to virB2 intergenic region or in virB2 reduced the detection of VirB5 to a greater extent than they did that of VirB12. A virB1 mutation also eliminates the transcription of virB12 in B suis [Ref6471:Höppner et al., 2005]. An infection assay with signature-tagged Brucella abortus mutants demonstrated that mutagenesis of the virB1 gene causes attenuation of virulence [Ref6471:Höppner et al., 2005]. GenBank: AE014292 transmission process Suggested label: pathogen transmission process transmission process A process that is the means during which the pathogen is transmitted directly or indirectly from its natural reservoir, a susceptible host or source to a new host. Transmission Ontology: http://purl.org/obo/owl/TRANS Suggested definition: A process by which a pathogen passes from one host organism to a second host organism of the same Species. transmission process Suggested label: indirect pathogen transmission process indirect Indirect transmission is a transmission process during which the pathogen is indirectly transferred from a reservoir, source or host to another host by intermediary vehicles, vectors or as airborne dust particles. indirect uterine cervix Lower, narrow portion of the uterus where it joins with the top end of the vagina. blood liver An exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes[GO]. kidney A paired organ which has the production of urine as its primary function. bone marrow flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells[WP]. vaccine A vaccine is a processed material with the function that when administered, it prevents or ameliorates a disorder in a target organism by inducing or modifying adaptive immune responses specific to the antigens in the vaccine. Brucella abortus DNA vaccine pcDNA-SOD A Brucella abortus vaccine that expresses Cu/Zn SOD with DNA plasmid pcDNA. PMID: 15039330. Brucella abortus vaccine RB51 Brucella abortus vaccine RB51 is a Brucella abortus vaccine that is licensed in the USA since 1992. Strain RB51 has a rough colonial morphology and lacks the O polysaccharide of LPS. (Schurig, G. G., R. M. Roop II, T. Bagchi, S. Boyle, D. Buhrman, and N. Sriranganathan. 1991. Biological properties of RB51: a stable rough strain of Brucella abortus. Vet. Microbiol. 28:171–188.) RB51 has an insertion within wboA gene that leads to the lack of Brucella LPS O-antigen and the rough phenotype.The wboA gene encoding a glycosyltransferase, an enzyme essential for the synthesis of O antigen, is disrupted by an IS711 element in B. abortus vaccine strain RB51. [Identification of an IS711 element interrupting the wboA gene of Brucella abortus vaccine strain RB51 and a PCR assay to distinguish strain RB51 from other Brucella species and strains. Vemulapalli R, McQuiston JR, Schurig GG, Sriranganathan N, Halling SM, Boyle SM. Clin Diagn Lab Immunol. 1999 Sep;6(5):760-4. PMID: 10473532] SRB51 Brucella RB-51 Brucella RB51 B. abortus RB51 Brucella abortus vaccine strain 19 Brucella strain-19 A live attenuated Brucella abortus vaccine that is licensed and used in many countries. Brucella S19 S19 has a 703 nucleotide deletion which interrupts both the coding regions of eryC (BAB2_0370) and eryD (BAB2_0369). The deletion affects the C terminal part of eryC and the N-terminal part of eryD proteins from B. abortus strains 2308 (BAB2_0369), 9–941 (BruAb2_0365) and B. suis (BRA0867). (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364660/) Brucella vaccine A vaccine that protects against Brucella that causes brucellosis in animals and humans. brucellosis vaccine Brucella abortus vaccine immunized an organismal quality that indicates an organism (e.g., human) is immunized against a disease. B. melitensis strain VTRM1 Brucella suis strain VTRS1 B. suis VTRS1 B. melitensis lipopolysaccharide vaccine B. melitensis LPS-GBOMP noncovalent complex vaccine B. melitensis LPS-GBOMP subunit vaccine Brucella abortus DNA vaccine encoding BCSP31, SOD and L7/L12 B. abortus DNA vaccine expressing BCSP31, SOD and L7/L12 Brucella abortus conjugate vaccine using L7/L12 recombinant B. abortus L7/L12 vaccine B. melitensis DNA vaccine encoding Omp31 B. melitensis bp26 deletion vaccine CGV26 Brucella CGV26 A B. melitensis vaccine that is recombinant B. melitensis Rev. 1 vaccine with the bp26 deletion. It has similar vaccine efficacy to Rev. 1. Its advantage compared to Rev. 1 is that this feature of bp26 deletion promotes diagnosis. PMID: 17070627. B. melitensis WR201 Brucella abortus bacA mutant B. abortus bacA mutant B. ovis microparticle subunit vaccine Brucella recombinant SurA protein vaccine Brucella recombinant SurA protein Brucella rSurA protein vaccine Brucella recombinant DnaK protein vaccine divalent DNA B. abortus vaccine using L7/L12 and Omp16 Brucella abortus DNA vaccine encoding L7/L12 and P39 B. abortus DNA vaccine encoding L7/L12 and P39 attenuated Brucella abortus with deletion of znuA microencapsulated B. melitensis mutant vaccine A B. melitensis vaccine that is composed of live Brucella melitensis attenuated mutant delivered using a microsphere delivery system. porin-S-LPS from B. abortus strain 2308 complex of porin and S-LPS from B. abortus strain 2308 Brucella abortus RB51WboA B. abortus RB51WboA recombinant O. anthropi 49237SOD B. melitensis Bp26 and Tf protein vaccine B. melitensis Bp26 and trigger factor B. melitensis P39 recombinant protein vaccine A Brucella subunit vaccine that uses recombinant Brucella melitensis 16M P39, a putative periplasmic binding protein. PMID: 11447155. recombinant chimera BLSOmp31 rBLSOmp31 Brucella abortus pcDNA-BLS B. abortus pcDNA-BLS escheriosome-mediated delivery of B. abortus L7/L12 escheriosome-encapsulated B. abortus L7/L12 B. melitensis DNA vaccine encoding Omp31 boosted with Omp31 pCIBLSOmp31 NPAP Brucella vaccine Brucella vaccine using nonpathogenic alphaproteobacteria protective antigen role Protective antigen is an antigen that stimulates protective immunity when used in vivo. vaccine preparation vaccine production vaccine generation vaccine preparation is a manufacturing process to produce a vaccine. B. melitensis Rev. 1 with P39 deletion B. melitensis Rev. 1 P39 deletion mutant A B. melitensis vaccine that is recombinant B. melitensis Rev. 1 vaccine with the p39 gene deletion. Brucella melitensis vaccine B. melitensis strain Rev. 1 Brucella melitensis Rev. 1 Brucella melitensis Rev 1 Brucella abortus strain RB51SOD B. abortus strain RB51SOD Brucella suis vaccine a Brucella vaccine against infection wtih B. suis Brucella suis strain 2 An orally administrable brucellosis vaccine that was was developed in China. It is effective for oral vaccination of sheep, goats, cattle and pigsPMID: 3541425. Brucella suis S2 Brucella abortus strain 45/20 B. abortus strain 45/20 Brucella abortus S19 with P39 deletion B. abortus S19 P39 deletion mutant A B. abortus vaccine that is recombinant B. abortus strain 19 vaccine with the p39 gene deletion. Brucella abortus conjugate vaccine a B. abortus vaccine that uses a conjugate vaccine format Brucella abortus recombinant vector vaccine a B. abortus vaccine that uses a recombinant vector. live attenuated Brucella vaccine live attenuated Brucella vaccine is a live attenuated vaccine that protects against a Brucella infection. live attenuated Brucella abortus vaccine live attenuated Brucella vaccine is a live attenuated vaccine that protects against a Brucella abortus infection. live attenuated Brucella melitensis vaccine live attenuated Brucella vaccine is a live attenuated vaccine that protects against a Brucella melitensis infection. live attenuated Brucella suis vaccine live attenuated Brucella vaccine is a live attenuated vaccine that protects against a Brucella melitensis infection. Brucella DNA vaccine encoding chimera BLSOmp31 pCIBLSOmp31 B. abortus HSA-L7/L12 Brucella abortus Human serum albumin (HAS)-L7/L12 B. abortus L7/L12 is a B. abortus subunit vaccine using L7/L12 that is formed by recombinant Human Serum Albumin (HAS)-L7/L12 fusion protein. B. melitensis Rev. 1 with bp26 and omp31 deletions CGV2631 B. melitensis bp26 and omp31 deletion vaccine is a Brucella melitensis vaccine that has double deletions of bp26 and omp31. pCIOmp31 pTargeTomp31 B. abortus L7/L12 fused to MBP B. abortus L7/L12 fused to MBP is a B. abortus subunit vaccine using L7/L12 that uses recombinant L7/L12 fused on maltose binding protein MBP. B. abortus BLS-L7/L12 recombinant Brucella BLS-L7/L12 fusion protein vaccine recombinant Brucella lumazine synthase and L7/L12 fusion protein vaccine B. abortus BLS-L7/L12 is a B. abortus subunit vaccine using L7/L12 that is made as a recombinant BLS-L7/L12 fusion protein vaccine. Brucella abortus subunit vaccine Brucella melitensis subunit vaccine Brucella abortus DNA vaccine Brucella melitensis DNA vaccine protective antigen Brucella abortus subunit vaccine using Bfr recombinant Brucella abortus Bfr protein vaccine Brucella BFR antigen vaccine Brucella abortus subunit vaccine using Omp16 Brucella abortus Omp16 vaccine B. melitensis DNA vaccine encoding Bp26 and Tf Brucella Abortus Strain 19, Live Culture Vaccine (USDA: 1251.01) Brucella Abortus Strain 19, Live Culture, Reduced Dose Vaccine (USDA: 1251.02) Brucella Abortus Strain RB-51, Live Culture Vaccine (USDA: 1261.00) B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA Brucella abortus exsA mutant vaccine B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA B. melitensis mucR mutant vaccine B. melitensis omp25 mutant vaccine B. melitensis omp31 mutant vaccine Brucella abortus pgk mutant vaccine Brucella abortus pgm mutant vaccine B. melitensis WR201 (16MΔpurEK) B. melitensis WR201 (16MΔpurEK) B. abortus and B. melitensis mutants with unmarked deletion of asp24, virB2, or manBA live attenuated B. abortus with deletion of znuA B. abortus DNA vaccine encoding RplL and Omp16 example to be eventually removed failed exploratory term Person:Alan Ruttenberg The term was used used in an attempt to structure part of the ontology but in retrospect failed to do a good job metadata complete Class has all its metadata, but is either not guaranteed to be in its final location in the asserted IS_A hierarchy or refers to another class that is not complete. organizational term term created to ease viewing/sort terms for development purpose, and will not be included in a release ready for release Class has undergone final review, is ready for use, and will be included in the next release. Any class lacking "ready_for_release" should be considered likely to change place in hierarchy, have its definition refined, or be obsoleted in the next release. Those classes deemed "ready_for_release" will also derived from a chain of ancestor classes that are also "ready_for_release." metadata incomplete Class is being worked on; however, the metadata (including definition) are not complete or sufficiently clear to the branch editors. uncurated Nothing done yet beyond assigning a unique class ID and proposing a preferred term. pending final vetting All definitions, placement in the asserted IS_A hierarchy and required minimal metadata are complete. The class is awaiting a final review by someone other than the definition editor. All definitions, placement in the asserted IS_A hierarchy and required minimal metadata are complete. The class is awaiting a final review by someone other than the term editor. core Core is an instance of a grouping of terms from an ontology or ontologies. It is used by the ontology to identify main classes. PERSON: Alan Ruttenberg PERSON: Melanie Courtot placeholder removed terms merged An editor note should explain what were the merged terms and the reason for the merge. term imported This is to be used when the original term has been replaced by a term imported from an other ontology. An editor note should indicate what is the URI of the new term to use. term split This is to be used when a term has been split in two or more new terms. An editor note should indicate the reason for the split and indicate the URIs of the new terms created. other This is to be used if none of the existing instances cover the reason for obsolescence. An editor note should indicate this new reason. We expect to be able to mine these new reasons and add instances as required. universal A Formal Theory of Substances, Qualities, and Universals, http://ontology.buffalo.edu/bfo/SQU.pdf Alan Ruttenberg Hard to give a definition for. Intuitively a "natural kind" rather than a collection of any old things, which a class is able to be, formally. At the meta level, universals are defined as positives, are disjoint with their siblings, have single asserted parents. defined class "definitions", in some readings, always are given by necessary and sufficient conditions. So one must be careful (and this is difficult sometimes) to distinguish between defined classes and universal. A defined class is a class that is defined by a set of logically necessary and sufficient conditions but is not a universal Alan Ruttenberg named class expression A named class expression is a logical expression that is given a name. The name can be used in place of the expression. Alan Ruttenberg named class expressions are used in order to have more concise logical definition but their extensions may not be interesting classes on their own. In languages such as OWL, with no provisions for macros, these show up as actuall classes. Tools may with to not show them as such, and to replace uses of the macros with their expansions to be replaced with external ontology term Alan Ruttenberg Terms with this status should eventually replaced with a term from another ontology. group:OBI requires discussion A term that is metadata complete, has been reviewed, and problems have been identified that require discussion before release. Such a term requires editor note(s) to identify the outstanding issues. Alan Ruttenberg group:OBI GACGAACGGAATTTTTCCAATCCC TGCCGATCACTTAAGGGCCTTCAT AAATCGCGTCCTTGCTGGTCTGA TGCCGATCACTTAAGGGCCTTCAT axiom holds for all times Person:Alan Ruttenberg To say that each spatiotemporal region s temporally_projects_onto some temporal region t is to say that t is the temporal extension of s. (axiom label in BFO2 Reference: [080-003]) To say that spatiotemporal region s spatially_projects_onto spatial region r at t is to say that r is the spatial extent of s at t. (axiom label in BFO2 Reference: [081-003]) To say that each spatiotemporal region s temporally_projects_onto some temporal region t is to say that t is the temporal extension of s. (axiom label in BFO2 Reference: [080-003]) To say that spatiotemporal region s spatially_projects_onto spatial region r at t is to say that r is the spatial extent of s at t. (axiom label in BFO2 Reference: [081-003])