MECHANISMS OF BARTONELLA VIRULENCE IN AIDS PATIENTS

(修订摘要) 这项拟议研究的长期目标是深入了解巴尔通体的致病机制，巴尔通体是艾滋病患者的一种机会性病原体。亨塞氏杆菌和昆塔纳杆菌是一种挑剔的革兰氏阴性细菌，会导致杆状血管瘤病(BA)，这是一种影响艾滋病毒感染患者的血管增生性病变。复发和/或持续性血流感染是昆塔纳杆菌感染的一种常见表现，这种感染发生在艾滋病毒感染的所有阶段，并可在人类持续数月。会导致虚弱甚至致命的后遗症。我们最近发现了巴尔通体的一种蛋白质，它与其他能够成功和持续感染人类宿主的细菌病原体的毒力决定因素具有许多共同的特征。这种蛋白似乎与巴尔通体在人类中的致病有关。 这一建议的直接目的是通过阐明昆塔纳巴尔通体蛋白的毒力特性，包括在体外和体内与宿主的相互作用，以及该蛋白在艾滋病患者分离株中表达的临床和分子相关性，来研究巴尔通体的致病机制。该项目的最终目标是在细菌和宿主分子和细胞水平上确定该蛋白在巴尔通体介导的HIV感染患者发病机制中的作用。

(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.