MECHANISMS OF BARTONELLA VIRULENCE IN AIDS PATIENTS

拟议研究的Ionq Range目标是深入了解糖尿病的致病机制。 巴尔通体，一种艾滋病患者的机会性病原体。B.henselae和B.Quintana是挑剔的，奶奶- 导致杆状血管瘤病(BA)的阴性细菌，BA是一种影响艾滋病毒的血管增殖性病变- 被感染的病人。复发和/或持续性血流感染是B组的常见表现。 昆塔纳病毒感染在HIV感染的所有阶段都会发生，并可在人类体内持续数月， 会导致虚弱甚至致命的后遗症。我们最近发现了一个编码外源基因的基因家族 巴尔通体的膜蛋白(OMP)在动物模型中随时间的差异表达， 显然是由于排列整齐、同源的一个或多个拷贝的重排和/或缺失 基因。我们随后发现，来自艾滋病毒感染患者的分离株含有不同的数量和 这个可变外膜蛋白(VOMP)家族的基因组合。巴托尼拉·冯普是 其他革兰氏阴性细菌中几种研究很好的OMP粘附素的同源物，包括YADA 耶尔森氏菌，它与细菌的其他毒力决定因素有许多共同的特征 能够成功且持久地感染人类宿主的病原体。这个Vomp家族 代表了第一个在体内发现的巴尔通体毒力因子，似乎是一种多功能蛋白质。 参与人类巴尔通体的致病过程。 这项建议的直接目标是研究巴尔通体的致病机制，通过 昆塔纳巴氏杆菌毒力特性的研究包括：1)巴尔通体 Quintana Vomp粘附素在体内外与寄主的相互作用；2)阶段变化和调节 Quintana巴尔通体vomp基因的表达；3)vomp基因的临床和分子相关性 艾滋病患者分离株的基因定位和表达。该项目的最终目标是确定 Vomp家族在Bartonelta介导的HIV感染患者发病机制中的作用 细菌和宿主分子和细胞水平。

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.