Sigma 54 and Vibrio cholerae Pathogenesis

Sigma 54 和霍乱弧菌发病机制

• 批准号: 7540929
• 负责人: Karl E Klose
• 金额: $ 16.45万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7540929
• 关键词: Address; Affect; Alleles; Bacteria; Behavior; Cell physiology; Cessation of life; Chemoreceptors; Chemotactic Factors; Chemotaxis; Cholera; Disease; Flagella; Genes; Genetic; Genetic Transcription; Health; Human; Intestines; Laboratories; Lead; Link; Microbial Biofilms; Pathogenesis; Polysaccharides; RNA polymerase sigma 54; Regulation; Role; Sigma Factor; Vibrio cholerae; Virulence; Virulence Factors; antimicrobial; cell motility; design; mutant; novel; prevent; research study

DESCRIPTION (provided by applicant): Cholera is a human diarrheal disease caused by the bacterium Vibrio cholerae. This disease remains a health threat for the majority of the world, causing thousands of deaths every year. Our laboratory has shown that the alternate sigma factor, sigma54, contributes to the virulence of V. cholerae. Sigma54 regulates multiple cellular processes, including flagellar and chemotaxis gene transcription. Both motility and chemotaxis have been shown by various means to contribute to V. cholerae virulence, but the mechanism(s) linking these behaviors to virulence has been elusive. We have shown that the activity of one of the sigma54-dependent activators, FlrC, regulates enhanced intestinal colonization as well as flagellar synthesis. Flagellar synthesis, in turn, regulates the expression of a polysaccharide (VPS) necessary for biofilm formation. VPS expression is modulated by another sigma54-dependent activator, VpsR. VpsR is also necessary for virulence factor expression and intestinal colonization. Thus sigma54 appears to contribute to flagellar synthesis, chemotaxis, biofilm formation, and virulence, in part through two different (54-dependent activators, FlrC and VpsR. This proposal will focus on the contributions of these two sigma54-dependent activators to virulence and biofilm formation, as well as address the contribution of chemotaxis, a CT54-dependent phenomenon, on V. cholerae virulence. Experiments are designed to: 1. Identify the factors that regulate FlrC activity, as well as the gene(s) regulated by FlrC that contribute to intestinal colonization. 2. Characterize the role of chemotaxis in V. cholerae virulence, focusing primarily on methyl-accepting chemoreceptors (MCPs), and 3. Analyze the contribution of VpsR to VPS expression and virulence factor expression. These experiments are designed to illuminate how sigma54 controls the virulence and environmental persistence (i.e., biofilm formation) of V. cholerae through two activators, FlrC and VpsR, and through chemotaxis. The results should lead to a deeper understanding of virulence mechanisms of V. cholerae, and facilitate the discovery of novel antimicrobial therapies that can prevent cholera.

描述（由申请人提供）：霍乱是一种由霍乱弧菌引起的人类腹泻病。这种疾病仍然对世界大多数人的健康构成威胁，每年导致数千人死亡。我们的实验室已证明替代 sigma 因子 sigma54 会增强霍乱弧菌的毒力。 Sigma54 调节多种细胞过程，包括鞭毛和趋化基因转录。多种方法已表明运动性和趋化性都会导致霍乱弧菌毒力，但将这些行为与毒力联系起来的机制一直难以捉摸。我们已经证明，sigma54 依赖性激活剂之一 FlrC 的活性可调节增强的肠道定植以及鞭毛合成。反过来，鞭毛合成调节生物膜形成所需的多糖（VPS）的表达。 VPS 表达由另一种 sigma54 依赖性激活剂 VpsR 调节。 VpsR 对于毒力因子表达和肠道定植也是必需的。因此，sigma54 似乎有助于鞭毛合成、趋化性、生物膜形成和毒力，部分是通过两种不同的（54 依赖性激活剂）FlrC 和 VpsR。本提案将重点关注这两种 sigma54 依赖性激活剂对毒力和生物膜的贡献形成，以及解决趋化性（一种 CT54 依赖性现象）对霍乱弧菌毒力的影响。 到： 1. 确定调节 FlrC 活性的因素，以及受 FlrC 调节且有助于肠道定植的基因。 2. 表征趋化性在霍乱弧菌毒力中的作用，主要关注甲基接受化学感受器 (MCP)，以及 3.分析VpsR对VPS表达和毒力因子表达的贡献。 这些实验旨在阐明 sigma54 如何通过两种激活剂 FlrC 和 VpsR 以及通过趋化性来控制霍乱弧菌的毒力和环境持久性（即生物膜形成）。这些结果应该有助于更深入地了解霍乱弧菌的毒力机制，并有助于发现可以预防霍乱的新型抗菌疗法。

项目成果

Role of Vibrio polysaccharide (vps) genes in VPS production, biofilm formation and Vibrio cholerae pathogenesis.

• DOI: 10.1099/mic.0.040196-0
• 发表时间: 2010-09
• 期刊: Microbiology (Reading, England)
• 作者: Fong JCN;Syed KA;Klose KE;Yildiz FH
• 通讯作者: Yildiz FH

Vibrio2005: the First International Conference on the Biology of Vibrios.

Vibrio2005：第一届弧菌生物学国际会议。

• DOI: 10.1128/jb.00141-06
• 发表时间: 2006
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Thompson,FabianoL;Klose,KarlE;AVIBGroup
• 通讯作者: AVIBGroup

Lipidation of an FlrC-dependent protein is required for enhanced intestinal colonization by Vibrio cholerae.

FlrC 依赖性蛋白的脂化是增强霍乱弧菌肠道定植所必需的。

• DOI: 10.1128/jb.00924-07
• 发表时间: 2008
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Morris,DavidC;Peng,Fen;Barker,JeffreyR;Klose,KarlE
• 通讯作者: Klose,KarlE

Identification of proinflammatory flagellin proteins in supernatants of Vibrio cholerae O1 by proteomics analysis.

通过蛋白质组学分析鉴定霍乱弧菌 O1 上清液中的促炎鞭毛蛋白。

• DOI: 10.1074/mcp.m600228-mcp200
• 发表时间: 2006
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Xicohtencatl-Cortés,Juan;Lyons,Sean;Chaparro,AdrianaP;Hernández,DianaR;Saldaña,Zeus;Ledesma,MariaA;Rendón,MaríaA;Gewirtz,AndrewT;Klose,KarlE;Girón,JorgeA
• 通讯作者: Girón,JorgeA

A bacterial two-hybrid system that utilizes Gateway cloning for rapid screening of protein-protein interactions.

一种细菌双杂交系统，利用 Gateway 克隆快速筛选蛋白质-蛋白质相互作用。

• DOI: 10.2144/000113539
• 发表时间: 2010
• 期刊: BioTechniques
• 影响因子: 2.7
• 作者: Karna,SLRajasekhar;Zogaj,Xhavit;Barker,JeffreyR;Seshu,Janakiram;Dove,SimonL;Klose,KarlE
• 通讯作者: Klose,KarlE