MECHANISMS OF BARTONELLA VIRULENCE IN AIDS PATIENTS

超出所提供的空间。该研究的Ionq范围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致病菌。B. henselae和B. quintana是挑剔的革兰氏阴性细菌，可引起细菌性血管瘤病（BA），这是一种影响HIV感染患者的血管增生性病变。复发性和/或持续性血液感染是金塔纳芽孢杆菌感染的常见表现，发生在HIV感染的所有阶段的患者中，可在人类中持续数月，导致衰弱甚至致命的后遗症。我们最近发现了一个编码巴尔通体外膜蛋白（OMP）的基因家族，该基因家族在动物模型中随着时间的推移而差异表达，显然是由于串联排列的同源基因的一个或多个拷贝的重排和/或删除。我们随后发现，来自hiv感染患者的分离物含有来自可变外膜蛋白（Vomp）家族的不同数量和不同组合的基因。巴尔通体呕吐物是其他革兰氏阴性细菌（包括耶尔森氏菌的YadA）中几种已得到充分研究的OMP粘附素的同源物，它与其他细菌病原体的毒力决定因素具有许多共同特征，这些特征能够成功并持续感染人类宿主。该Vomp家族是在体内发现的第一个巴尔通体毒力因子，似乎是一种参与人类巴尔通体发病的多功能蛋白。本研究的直接目的是通过阐明昆塔纳巴尔通体呕吐物的毒力特性来研究巴尔通体的发病机制，包括表征：1)昆塔纳巴尔通体呕吐物在体内和体外与宿主的粘附素相互作用；2)金塔那巴尔通体呕吐物基因的期相变异及表达调控；3)艾滋病患者分离株呕吐物基因位点及表达的临床与分子相关性。该项目的最终目标是确定vmp家族在细菌和宿主分子和细胞水平上对巴尔通体介导的hiv感染患者发病机制的贡献。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================