期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 37, 页码 13630-13635出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0405284101
关键词
phase variation; multifunctional adhesin; collagen binding; bloodstream infection; YadA homolog
资金
- NIAID NIH HHS [R01 AI043703, R01 AI 43703, AI 52813, R01 AI052813] Funding Source: Medline
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 outermembrane 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 multi-gene family, they are variably expressed, and different virulence properties are attributable to individual Vomp family members.
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