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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(申请人提供)：耶尔森氏菌属细菌导致多种人类疾病。鼠疫杆菌导致了臭名昭著的瘟疫，由于可能被生物恐怖分子利用，这种疾病重新引起了人们的注意。相比之下，假结核和小肠结肠炎耶尔森菌主要引起胃肠道疾病。然而，尽管疾病症状不同，但这些致病耶尔森菌物种密切相关，并拥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，包括第一个广泛存在的三型分泌系统(T3SS)的例子。所有T3SS的关键成分是一种称为分泌素的外膜成孔蛋白。然而，分泌素的产生会导致细菌细胞被膜应激。这对小肠结肠炎耶尔森菌是致命的，除非一种称为噬菌体休克蛋白(PSP)系统的关键应激反应起作用。因此，小肠结肠炎耶尔森菌的PSP系统对致病力是必不可少的。此外，PSP系统对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它的核心成分，并确定了它们在调节和逆境耐受中的作用。我们未来的一些工作将集中在Ye毒力所需的PSP系统的两个关键方面：它是如何激活的，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)，它既能激活PSP基因的表达，又能抑制PSP缺失菌株的分泌素敏感性。该基因可能指导细胞快速生长时产生53个氨基酸的细胞膜蛋白，或在细胞进入稳定期时产生rpos诱导的非编码RNA。我们想要了解YE0566是如何诱导PSP系统的，以及当PSP系统缺失时，它是如何抑制分泌素敏感性的。为了解决我们的所有目标，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蛋白如何阻止分泌素渗透细胞膜；(3)研究YE0566的调节和功能。除了小肠结肠炎耶尔森菌外，这些研究还具有广泛的意义，因为对毒力至关重要的分泌素系统、PSP系统和YE0566同源物在医学上重要的细菌中广泛存在。