THE SALMONELLA TYPHIMURIUM SIGMAE REGULON

鼠伤寒沙门氏菌调节因子

• 批准号: 7033244
• 负责人: Ferric C Fang
• 金额: $ 38.88万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033244
• 关键词: Salmonella infections; Salmonella typhimurium; acidity /alkalinity; antiinfective agents; bacteria infection mechanism; bacterial genetics; bacterial proteins; biological signal transduction; gene expression; gene mutation; genetic regulation; genetic regulatory element; host organism interaction; laboratory mouse; macrophage; oxidative stress; polymerase chain reaction; transcription factor; virulence

DESCRIPTION (provided by applicant): The alternative sigma factor sigmaE plays a central role in Salmonella pathogenesis. In the initial project period, we have found that Salmonella mutants lacking sigmaE exhibit enhanced susceptibility to oxidative stress and antimicrobial peptides, reduced acid tolerance, deficient expression of virulence genes, impaired survival in phagocytic cells and markedly diminished virulence in mice. Furthermore we have identified novel sigmaE-dependent loci, demonstrated that sigmaE interacts with the other four alternative sigma factors in Salmonella, and discovered that sigmaE complements the actions of the phage shock (psp) response in maintaining proton motive force. In this competing renewal application, our specific aims are to: [1] Comprehensively characterize the regulatory networks interconnecting the alternative sigma factors of Salmonella; [2] Analyze the mechanism of sigmaE activation and its stimulation of Salmonella Pathogenicity Island 2 (SPI-2) gene expression in response to acid pH; [3] Examine the complementary actions of sigmaE and PspA in promoting resistance to antimicrobial peptides and the maintenance of proton motive force; [4] Assess the roles of specific sigmaE -dependent genes in resistance to acid pH, oxidative stress, antimicrobial peptides and virulence. Recent work in our laboratory and many others has revealed the enormous complexity and interconnectedness of bacterial regulatory networks. Through the proposed studies, we hope to provide a detailed mechanistic understanding of one of the most important regulatory pathways in Salmonella and to reveal novel insights into its physiologic functions.

描述（由申请人提供）：替代 sigma 因子 sigmaE 在沙门氏菌发病机制中发挥着核心作用。在项目初期，我们发现缺乏sigmaE的沙门氏菌突变体对氧化应激和抗菌肽的敏感性增强、耐酸能力降低、毒力基因表达缺陷、吞噬细胞存活受损以及对小鼠的毒力显着降低。此外，我们还鉴定了新的 sigmaE 依赖性位点，证明 sigmaE 与沙门氏菌中的其他四种替代 sigma 因子相互作用，并发现 sigmaE 补充了噬菌体休克 (psp) 反应在维持质子动力方面的作用。在这个竞争性续订申请中，我们的具体目标是： [1] 全面描述沙门氏菌替代西格玛因子相互连接的调控网络； [2] 分析酸性pH条件下sigmaE激活及其对沙门氏菌致病岛2（SPI-2）基因表达的刺激机制； [3] 研究sigmaE和PspA在促进抗菌肽耐药性和维持质子动力方面的互补作用； [4] 评估特定 sigmaE 依赖性基因在抵抗酸性 pH、氧化应激、抗菌肽和毒力方面的作用。 我们实验室和许多其他实验室最近的工作揭示了细菌调节网络的巨大复杂性和相互关联性。通过拟议的研究，我们希望对沙门氏菌最重要的调节途径之一提供详细的机制理解，并揭示其生理功能的新见解。