Regulation of virulence factors in Bartonella henselae

汉赛巴尔通体毒力因子的调控

• 批准号: 8111405
• 负责人: BURT E ANDERSON
• 金额: $ 14.55万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-26 至 2012-01-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111405
• 关键词: Angiogenic Factor; Antigens; Bacillary Angiomatosis; Bacteria; Bacterial Adhesins; Bacterial Genes; Bacterial Typing; Bartonella; Bartonella henselae; Binding; Biological Assay; Blood Vessels; Cat-Scratch Disease; Cells; Clinical; DNA; DNA Microarray Chip; DNA delivery; Data; Disease; Effector Cell; Endothelial Cells; Environment; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Goals; Immunocompromised Host; Individual; Infection; Infection prevention; Infectious Agent; Laboratories; Lesion; Life; Mediating; Modeling; Operon; Organ; Pathogenesis; Patients; Peptides; Phenotype; Play; Process; Production; Proteins; Recruitment Activity; Regulation; Regulator Genes; Reporting; Research; Role; Signal Transduction; Surface; Syndrome; System; Systemic infection; Testing; Transcriptional Regulation; Type IV Secretion System Pathway; Up-Regulation; Vascular Endothelial Growth Factors; Virulence; Virulence Factors; Visceral; angiogenesis; antimicrobial; base; gene therapy; genetic regulatory protein; in vivo; knockout gene; mutant; overexpression; promoter; skin lesion

DESCRIPTION (provided by applicant): 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 responsible 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 system OmpR/EnvZ of B. henselae is at least in part responsible 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 patients 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. Narrative Project Description The bacterium Bartonella henselae causes a variety of disease syndromes including severe life-threatening infections in some patients, particularly in immunocompromised individuals. The unique aspect of this severe disease is the proliferation of blood vessels, or angiogenesis. This project seeks to better understand how the genes of this bacterium are controlled to cause this angiogenesis. Characterization of a gene regulatory system that controls bacterial virulence factors may prove to be a valuable target for antimicrobial therapy to prevent infections caused by B. henselae.

描述（由申请人提供）：Bartonella henselae细菌会引起各种疾病综合征，包括某些患者的严重全身感染，特别是在免疫功能低下的个体中。这种新兴的感染剂的一种表现是杆菌血管瘤病，其特征是受感染患者的皮肤和内脏器官的血管增殖性病变的存在。该项目的目的是检验中心假设：Henselae B. henselae利用对几种毒力因子基因的坐标调节来增强其促进血管生成的能力。在Henselae中已经发现了至少两个重要的毒力因子，它们在引起血管生成方面发挥了作用。第一个是编码IV型分泌系统的VIRB操纵子，该系统负责递送对内皮细胞作用的效应蛋白以促进其扩展的生存。第二个是henselae表面上的主要粘附素BADA，并且已被证明在感染细胞中诱导血管内皮生长因子分泌很重要。我们的初步数据表明，henselae的两个组分调节系统OMPR/Envz至少部分负责调节这些基因。提出了以下特定目的来检验假设。 1）定义OMPR与VirB操纵子的表达和表达之间的相关性，2）表征ompr/envz上调的ViRB的机制，以及3）识别在OMPR/Envz控制下的其他毒力因子基因。这些研究应有助于我们了解某些患者的细菌如何以及为什么会导致其他导致血管生成病变的患者的生命感染。此外，控制细菌毒力因子的基因调节系统的表征可能被证明是抗菌治疗的宝贵靶标。该项目的应用产物是对IV型IV型分泌系统基因的调节机制的描述。这些信息可能会证明在将来利用该分泌系统用于将DNA和蛋白质用于基因治疗的细胞的尝试中很有价值。叙事项目描述Bartonella henselae细菌引起了多种疾病综合征，包括某些患者，特别是免疫功能低下的个体，包括严重威胁生命的感染。这种严重疾病的独特方面是血管的增殖或血管生成。该项目旨在更好地了解该细菌的基因如何控制这种血管生成。控制细菌毒力因子的基因调节系统的表征可能被证明是抗菌治疗的宝贵靶标，以防止henselae引起的感染。