Regulation of virulence factos in Bartonella henselae

亨氏巴尔通体细菌可引起多种疾病症状，包括严重的全身性 在一些患者中，特别是在免疫功能低下的人中感染。这一点的一个表现就是 新出现的感染性病原体是以血管的存在为特征的细菌性血管瘤病。 感染患者皮肤和内脏器官的增生性病变。该项目的目标是测试 中心假说是亨氏伯氏杆菌利用几个毒力因子基因的协同调节来 增强其促进血管生成的能力。至少已经确定了两个重要的毒力因素 在导致血管生成方面发挥作用的亨塞氏杆菌。第一个是编码IV型病毒的VIRB操纵子 负责传递作用于内皮细胞的效应蛋白以促进 延长了他们的生存时间。第二种是主要的粘附素Bada，它位于亨斯莱的表面，具有 已被证明在诱导感染细胞分泌血管内皮生长因子方面具有重要作用。我们的 初步数据表明，亨氏假单胞菌的OmpR/EnvZ双组分调控系统至少在 对这些基因的调控负有部分责任。为了检验这一假设，本文提出了以下具体目标； 1)明确ompR和envZ表达与VIRB操纵子表达的相关性；2) 描述VIRB的ompR/envZ上调的机制，以及3)鉴定其他毒力 OmpR/envZ调控下的因子基因。这些研究应该有助于我们理解这是如何以及为什么 细菌在一些患者中会导致轻微的疾病，在其他患者中会导致危及生命的感染，从而导致 血管新生损伤。此外，控制细菌的基因调控系统的特征 毒力因子可能被证明是抗菌治疗的一个有价值的靶点。它的一个应用产品 该项目描述了VIRB IV型分泌系统基因的调节机制。是这样的 这些信息可能会被证明是有价值的，在未来试图利用这种分泌系统传递 以DNA和蛋白质为靶细胞进行基因治疗。

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.