title: A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella quintana.
abstract: Bartonella species are fastidious, Gram-negative human pathogens that can persist in the host bloodstream for years and bind to and invade several types of host cells. For many pathogens, adhesion to host cells and extracellular matrix (ECM) components is a critical virulence determinant. Bacteria often vary expression of surface adhesins by phase or antigenic variation to subvert the host immune response and permit adaptive interaction with different host structures. We developed a macaque animal model for Bartonella quintana infection to detect changes in bacterial outer-membrane proteins (OMP) during prolonged bloodstream infection. We identified a gene family encoding four highly conserved, 100-kDa, variably expressed OMP (Vomp), two of which function as adhesins. The variable expression of Vomp family members appears to be mediated by deletion of one or more vomp genes during chronic bloodstream infection. vomp deletion was observed also in isolates from humans with chronic B. quintana infection. The Vomp are closely related to the afimbrial adhesin, YadA, a virulence factor of Yersinia enterocolitica. The surface-expressed Vomp contain conserved structural features of YadA, including collagen-binding motifs. We demonstrate that the B. quintana Vomp are multifunctional OMP involved in binding to collagen and autoaggregation: VompC confers the ability to bind collagen IV, and VompA is necessary and sufficient for autoaggregation. The B. quintana Vomp are members of the newly recognized family of YadA-like trimeric autotransporters; the Vomp constitute a multigene family, they are variably expressed, and different virulence properties are attributable to individual Vomp family members.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California-San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0654.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Chomel
authors.forename: Maureen K
authors.initials: MK
authors.lastname: Schau
authors.forename: Jeanna S
authors.initials: JS
authors.lastname: Goo
authors.forename: Sara
authors.initials: S
authors.lastname: Droz
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kelminson
authors.forename: Smitha S
authors.initials: SS
authors.lastname: George
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lerche
authors.forename: Jane E
authors.initials: JE
authors.lastname: Koehler
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018413:Bartonella quintana / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D017124:Conserved Sequence; D015180:Electrophoresis, Gel, Two-Dimensional; D015321:Gene Rearrangement; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D023421:Models, Animal; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D014205:Trench Fever / Q000097:blood / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D003094:Collagen