The Psp response of Yersina enterocolitica

小肠结肠炎耶尔森氏菌的 Psp 反应

• 批准号: 8695130
• 负责人: ANDREW J. DARWIN
• 金额: $ 39.96万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695130
• 关键词: Address; Affect; Amino Acids; Bacteria; Bacteria sigma factor KatF protein; Bacterial Proteins; Bacteriophages; Binding; Cell Death; Cell Membrane Permeability; Cell membrane; Cells; Cytoplasm; Data; Disease; Event; Functional RNA; Funding; Future; Gastroenteritis; Gastrointestinal Diseases; Gene Expression; Genes; Goals; Health; Homologous Gene; Human; Investigation; Link; Location; Membrane; Membrane Proteins; Messenger RNA; Microbial Biofilms; Modeling; Mus; Null Lymphocytes; Pasteurella pseudotuberculosis; Pathogenesis; Phase; Plague; Process; Production; Proteins; RNA; Regulation; Research; Role; Secretin; Sensory; Shock; Signal Transduction; Small RNA; Stress; Symptoms; System; Testing; Toxic effect; Transcript; Virulence; Work; Yersinia; Yersinia enterocolitica; Yersinia pestis; attenuation; biological adaptation to stress; cell envelope; design; human disease; insight; novel therapeutics; overexpression; pathogen; porin; prevent; public health relevance; response; stress tolerance

DESCRIPTION (provided by applicant): Bacteria of the genus Yersinia are responsible for a variety of human diseases. Y. pestis causes the infamous disease Plague, which regained prominence due to its potential use by bioterrorists. In contrast, Y. pseudotuberculosis and Y. enterocolitica cause primarily gastrointestinal disease. However, despite the differences in disease symptoms, these pathogenic Yersinia species are closely related and share several common virulence determinants. Yersinia studies have provided fundamental insights into bacterial pathogenesis, including the first example of the widespread type three secretion system (T3SS). A critical component of all T3SSs is an outer membrane pore-forming protein known as a secretin. However, secretin production can cause bacterial cell envelope stress. This is lethal to Y. enterocolitica unless a critical stress response known as the phage shock protein (Psp) system is functional. As a result, the Psp system of Y. enterocolitica is essential for virulence. Furthermore, the Psp system is also important for virulence and additional health-related processes in other bacteria. Our studies of the Psp system have identified its core components and defined their roles in regulation and stress tolerance. Some of our future work will focus on the two critical aspects of the Psp system required for Ye virulence: how is it activated and how is T3SS-induced cell death prevented? We have also identified a highly conserved gene (YE0566) that can both activate psp gene expression and suppress secretin-sensitivity in a psp null strain. This gene might direct the production of a 53 amino acid cytoplasmic membrane protein when cells are growing rapidly or an RpoS- induced non-coding RNA when cells enter stationary phase. We want to understand how YE0566 induces the Psp system and how it suppresses secretin-sensitivity when the Psp system is absent. To address all of our goals we propose to: (1) Investigate how an inducing signal is detected and transduced by the Psp system; (2) Analyze how the PspB and PspC proteins prevent secretins from permeabilizing the cytoplasmic membrane; (3) Investigate the regulation and function of YE0566. These studies also have broad significance beyond Y. enterocolitica because secretin-containing systems critical for virulence, the Psp system, and YE0566 homologues are widespread in medically important bacteria.

描述（由申请人提供）：耶尔森氏菌属细菌是多种人类疾病的致病菌。Y.鼠疫引起臭名昭著的疾病瘟疫，由于其可能被生物恐怖分子使用而重新引起人们的注意。相比之下，Y. pseudotuberculosis和Y.小肠结肠炎主要引起胃肠道疾病。然而，尽管疾病症状存在差异，但这些致病性耶尔森氏菌属物种密切相关，并具有几个共同的毒力决定因素。耶尔森氏菌的研究为细菌的发病机制提供了基本的见解，包括广泛分布的第三型分泌系统（T3 SS）的第一个例子。所有T3 SS的一个关键组成部分是一种称为分泌素的外膜孔形成蛋白。然而，分泌素的产生可引起细菌细胞被膜应激。这对Y来说是致命的。除非被称为噬菌体休克蛋白（Psp）系统的关键应激反应是功能性的，否则小肠结肠炎菌是不可能的。因此，Y.小肠结肠炎菌对毒性至关重要。此外，Psp系统对其他细菌的毒力和其他健康相关过程也很重要。我们对Psp系统的研究已经确定了它的核心组成部分，并确定了它们在调节和应激耐受中的作用。我们未来的一些工作将集中在叶病毒所需的Psp系统的两个关键方面：它是如何被激活的，以及如何防止T3 SS诱导的细胞死亡？我们还确定了一个高度保守的基因（YE 0566），既可以激活psp基因表达和抑制分泌素敏感性的psp空菌株。当细胞快速生长时，该基因可能指导53个氨基酸的细胞质膜蛋白的产生，或者当细胞进入稳定期时，该基因可能指导RpoS诱导的非编码RNA的产生。我们想了解YE 0566如何诱导Psp系统，以及当Psp系统不存在时，它如何抑制分泌素敏感性。为了解决我们所有的目标，我们建议：（1）研究诱导信号是如何检测和转导的Psp系统;（2）分析PspB和PspC蛋白如何防止分泌素透化细胞质膜;（3）研究YE 0566的调节和功能。这些研究在Y.这是因为对毒力至关重要的含分泌素系统、Psp系统和YE 0566同源物广泛存在于医学上重要的细菌中。