Regulation of virulence factos in Bartonella henselae

汉赛巴尔通体细菌可引起多种疾病综合征，包括严重的全身性疾病 一些患者，特别是免疫功能低下的个体发生感染。这一点的体现之一 新出现的传染源是杆菌性血管瘤病，其特征是存在血管 感染患者皮肤和内脏器官的增殖性病变。该项目的目标是测试 中心假设是 B. henselae 利用多个毒力因子基因的协调调节 增强其促进血管生成的能力。至少已鉴定出两个重要的毒力因子 B. henselae 在引起血管生成中发挥作用。第一个是编码 IV 型的 virB 操纵子 分泌系统，负责传递作用于内皮细胞的效应蛋白，以促进 他们的生存期延长了。第二个是 B. henselae 表面的主要粘附素 BadA，具有 已被证明对于诱导受感染细胞分泌血管内皮生长因子很重要。我们的 初步数据表明 B. henselae 的双组分调控系统 OmpR/EnvZ 至少处于 部分负责这些基因的调节。提出以下具体目标来检验假设； 1) 定义 ompR 和 envZ 表达与 virB 操纵子表达之间的相关性，2) 表征 virB 的 ompR/envZ 上调机制，以及 3) 确定其他毒力 ompR/envZ 控制下的因子基因。这些研究应该帮助我们理解这是如何以及为何发生的 细菌会导致一些患者出现轻微疾病，并导致其他患者出现危及生命的感染，从而导致 血管生成病变。此外，控制细菌的基因调控系统的表征 毒力因子可能被证明是抗菌治疗的一个有价值的目标。本发明的应用产品 项目描述了virB IV型分泌系统基因的调控机制。这样的 在未来尝试利用这种分泌系统来传递信息时，信息可能会被证明是有价值的。 DNA 和蛋白质用于基因治疗的靶细胞。

The bacterium Bartonella henselae causes a variety of disease syndromes including severe systemic infections in some patients, particularly in immunocompromised individuals. One manifestation of this emerging infectious agent is bacillary angiomatosis which is characterized by the presence of vascular proliferative lesions of the skin and visceral organs in infected patients. The goal of this project is to test the central hypothesis that B. henselae utilizes coordinate regulation of several virulence factor genes to enhance it's ability to promote angiogenesis. At least two important virulence factors have been identified in B. henselae that play a role in causing angiogenesis. The first is the virB operon that encodes a type IV secretion system that is resposible for delivery of the effector proteins that act on endothelial cells to promote their extended survival. The second is the major adhesin BadA that is on the surface of B. henselae and has been shown to be important in inducing vascular endothelial growth factor secretion in infected cells. Our preliminary data suggest that the two-component regulatory sytem OmpR/EnvZ of B. henselae is at least in part resposible for regulation of these genes. The following specific aims are proposed to test the hypothesis; 1) define the correlation between ompR and envZ expression and expression of the virB operon, 2) characterize the mechanism involved in ompR/envZ upregulation of virB, and 3) identify other virulence factor genes under control of ompR/envZ. These studies should help us understand how and why this bacterium causes mild disease in some patients and life-threatening infections in other pateints resulting in angiogenic lesions. Furthermore, characterization of a gene regulatory system that controls bacterial virulence factors may prove to be a valuable target for antimicrobial therapy. An applied product of this project is the description of the regulatory mechanism of the virB type IV secretion system genes. Such information may prove valuable in future attempts to harness the use of this secretion system for delivery of DNA and protein to target cells for gene therapy.