The Ionq range objective of the proposed study is to gain insight into the pathogenic mechanisms of Bartonella, an opportunistic pathogen of AIDS patients. B. henselae and B. quintana are fastidious, gram- negative bacteria that cause bacillary angiomatosis (BA), a vascular proliferative lesion affecting HIV- infected patients. Relapsing and/or persistent bloodstream infection is a frequent manifestation of B. quintana infection that occurs in patients at all stages of HIV infection and can last for months in humans, causing debilitating and even fatal sequelae. We recently identified a gene family encoding an outer membrane protein (OMP) of Bartonella that is differentially expressed over time in an animal model, apparently due to rearrangement and/or deletion of one or more copies of tandemly-arranged, homologous genes. We subsequently found that isolates from HIV-infected patients contain different numbers and combinations of genes from this variable outer membrane protein (Vomp) family. The Bartonella Vomp is a homologue of several well-studied OMP adhesins in other gram-negative bacteria, including the YadA of Yersinia, and it has a number of characteristics in common with other virulence determinants of bacterial pathogens that are able to successfully and persistently infect the human host. This Vomp family represents the first Bartonella virulence factor identified in vivo, and appears to be a multifunctional protein involved in Bartonella pathogenesis in humans. The immediate objective of this proposal is to study the mechanisms of Bartonella pathogenesis by elucidating the virulence properties of the B. quintana Vomp including characterization of: 1)the Bartonella quintana Vomp adhesin interactions with the host in vitro and in vivo; 2) phase variation and regulation of expression of the Bartonella quintana vomp genes; and 3) clinical and molecular correlation of vomp gene locus and expression in isolates from AIDS patients. The ultimate goal of this project is to identify the contribution of the Vomp family to Bartonelta-mediated pathogenesis in HIV-infected patients at the bacterial and host molecular and cellular levels.
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