(Revised Abstract) The long 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 protein of Bartonella that 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 protein appears to be 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 protein, including characterization of the interactions with the host in vitro and in vivo, and the clinical and molecular correlation of expression of this protein in isolates from AIDS patients. The ultimate goal of this project is to identify the contribution of this protein to Bartonella-mediated pathogenesis in HIV-infected patients at the bacterial and host molecular and cellular levels.
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