Regulation of virulence factos in Bartonella henselae

汉赛巴尔通体（Bartonella henselae）细菌引起多种疾病综合征，包括严重的全身性 在某些患者中，特别是在免疫功能低下的个体中，其中的一个表现 新出现的感染因子是杆菌性血管瘤病，其特征在于存在血管性血管瘤。 感染患者皮肤和内脏器官的增生性病变。本项目的目标是测试 中心假设B.汉赛线虫利用几种毒力因子基因的协调调节， 增强其促进血管生成的能力。至少有两个重要的毒力因子已被确定， B。在引起血管生成中起作用的Henselae。第一个是virB操纵子，它编码IV型 分泌系统，其负责递送作用于内皮细胞以促进内皮细胞增殖的效应蛋白。 延长生存期。第二个是位于B表面的主要粘附素BadA。汉塞莱和哈斯 已显示在感染细胞中诱导血管内皮生长因子分泌中是重要的。我们 初步数据表明，B. henselae至少在 部分负责这些基因的调控。为检验这一假设，提出了以下具体目标： 1)确定ompR和envZ表达与virB操纵子表达之间的相关性，2） 表征参与ompR/envZ上调virB的机制，以及3）鉴定其他毒力 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什么的。 细菌在一些患者中引起轻微疾病，在另一些患者中引起危及生命的感染， 血管生成性病变此外，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微生物治疗的有价值的靶点。这一应用产品 项目是描述virB IV型分泌系统基因的调控机制。等 这些信息可能在未来尝试利用这种分泌系统来递送 DNA和蛋白质靶向细胞进行基因治疗。

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.