MECHANISMS OF BARTONELLA VIRULENCE IN AIDS PATIENTS

（修订摘要） 该研究的长期目标是深入了解艾滋病患者的条件致病菌巴尔通体的致病机制。 B。henselae和B.昆塔纳是苛养的革兰氏阴性细菌，其引起杆菌性血管瘤病（BA），一种影响HIV感染患者的血管增生性病变。 复发性和/或持续性血流感染是B的常见表现。在艾滋病毒感染的各个阶段的患者中发生的五他那感染，在人类中可持续数月。导致虚弱甚至致命的后遗症。 我们最近鉴定了巴尔通体的一种蛋白质，该蛋白质与能够成功和持续感染人类宿主的细菌病原体的其他毒力决定因子具有许多共同特征。 这种蛋白质似乎参与人类巴尔通体的发病机制。 该建议的直接目标是通过阐明B的毒力特性来研究巴尔通体的致病机制。quintana蛋白，包括在体外和体内与宿主的相互作用的表征，以及这种蛋白在艾滋病患者分离株中表达的临床和分子相关性。 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对HIV感染患者中巴尔通体介导的发病机制的贡献。

(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.