HOST CELL INTERACTIONS BY PATHOGENIC BORRELIAE

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DESCRIPTION (Adapted from the Applicant's Abstract): Borrelia burgdorferi is the causative agent of Lyme disease, and B. hermsii and B. turicatae are causative agents of tick-borne relapsing fever. Pathogen-host cell interactions are thought to be critical determinants of the site and severity of infection, and Dr. Leong's group has focused on Borreliae recognition of two classes of host cell molecules: (1) glycosaminoglycans (GAGs); and (2) integrins and their associated proteins. For B. burgdorferi, they have found that differences in GAG recognition were associated with differences in host cell type-specific binding, and identified a surface protein, Bgp, that may be the major B. burgdorferi GAG receptor. This bacterium also recognizes the activation-dependent platelet integrin alphaIIbbeta3 and thereby selectively binds to activated (vs. resting) platelets. This integrin-binding activity is predicted to target the Lyme disease spirochete to the vessel wall at sites of platelet adherence, and could explain a salient feature of Lyme disease: vascular pathology of the arterial circulation. In Dr. Leong's studies of relapsing fever spirochetes, high-level GAG-binding correlated with high-level growth in the bloodstream, and a variable major protein, VspB, promoted attachment to GAGs. Additionally, in contrast to B. burgdorferi, B. hermsii bound and activated resting platelets. The platelet activation activity is apparently mediated by the integrin-associated platelet-signaling molecule CD9. Dr. Leong speculates that prior to the development of an antibody response, attachment of relapsing fever spirochetes to the vessel wall, either directly via GAGs or indirectly, via activated and adherent platelets, could diminish the clearance of bacteria from the bloodstream by the reticuloendothelial system. Continued replication by these adherent bacteria would result in high level bacterial seeding of the bloodstream. Interaction of spirochetes with platelets could also contribute to thrombocytopenia, a common manifestations of relapsing fever.