The Psp response of Yersina enterocolitica

小肠结肠炎耶尔森氏菌的 Psp 反应

基本信息

批准号：
9258378
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
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-03-15 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9258378
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 Funding Future Gastroenteritis Gastrointestinal Diseases Gene Expression Genes Goals Health Homologous Gene Human Investigation Link Location Medical Membrane Membrane Proteins Messenger RNA Microbial Biofilms Modeling Mus Null Lymphocytes Pasteurella pseudotuberculosis Pathogenesis Pathogenicity Phase Plague Process Production Proteins RNA Regulation Research Role Secretin Sensory Shock Signal Transduction Small RNA Stress Symptoms System Testing Toxic effect Transcript Untranslated RNA VDAC1 gene Virulence Work Yersinia Yersinia enterocolitica Yersinia pestis attenuation biological adaptation to stress cell envelope design human disease insight novel therapeutic intervention overexpression pathogen prevent public health relevance response stress tolerance

项目摘要

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）：耶尔森氏菌属细菌导致多种人类疾病。鼠疫耶尔森氏菌引起臭名昭著的鼠疫疾病，由于其可能被生物恐怖分子利用，鼠疫重新引起人们的关注。相反，假结核耶尔森氏菌和小肠结肠炎耶尔森氏菌主要引起胃肠道疾病。然而，尽管疾病症状存在差异，这些致病性耶尔森菌物种密切相关，并具有一些共同的毒力决定因素。耶尔森氏菌研究为细菌发病机制提供了基本见解，包括广泛传播的三型分泌系统（T3SS）的第一个例子。所有 T3SS 的一个关键成分是一种称为促胰液素的外膜成孔蛋白。然而，促胰液素的产生会引起细菌细胞包膜应激。这对于小肠结肠炎耶尔森氏菌来说是致命的，除非称为噬菌体休克蛋白（Psp）系统的关键应激反应发挥作用。因此，小肠结肠炎耶尔森氏菌的 Psp 系统对于其毒力至关重要。此外，Psp 系统对于其他细菌的毒力和其他与健康相关的过程也很重要。我们对 Psp 系统的研究已经确定了其核心组件，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于 Ye 毒力所需的 Psp 系统的两个关键方面：它是如何被激活的以及如何防止 T3SS 诱导的细胞死亡？我们还鉴定了一个高度保守的基因 (YE0566)，它既可以激活 psp 基因表达，又可以抑制 psp 无效菌株中的促胰液素敏感性。当细胞快速生长时，该基因可能指导产生 53 个氨基酸的细胞质膜蛋白；当细胞进入静止期时，该基因可能指导产生 RpoS 诱导的非编码 RNA。我们想要了解 YE0566 如何诱导 Psp 系统以及当 Psp 系统不存在时它如何抑制促胰液素敏感性。为了实现我们的所有目标，我们建议：（1）研究 Psp 系统如何检测和转导诱导信号； (2)分析PspB和PspC蛋白如何阻止促胰液素透细胞质膜； (3)研究YE0566的调控和功能。这些研究在小肠结肠炎耶尔森氏菌之外也具有广泛的意义，因为对毒力至关重要的含促胰液素系统、Psp 系统和 YE0566 同源物在医学上重要的细菌中广泛存在。