The Psp response of Yersina enterocolitica

描述（由申请人提供）：耶尔森氏菌属细菌是多种人类疾病的罪魁祸首。鼠疫杆菌引起臭名昭著的瘟疫，由于它可能被生物恐怖分子利用而重新引起人们的注意。相反，假结核杆菌和小肠结肠炎杆菌主要引起胃肠道疾病。然而，尽管疾病症状不同，这些致病性耶尔森菌物种密切相关，并有几个共同的毒力决定因素。耶尔森菌的研究为细菌的发病机制提供了基本的见解，包括广泛存在的第三型分泌系统（T3SS）的第一个例子。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，分泌素的产生会引起细菌的细胞膜压力。这对小肠结肠炎耶氏菌是致命的，除非被称为噬菌体休克蛋白（Psp）系统的临界应激反应起作用。因此，小肠结肠炎耶氏菌的Psp系统对其毒力至关重要。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其核心成分，并定义了它们在调节和应力耐受性中的作用。我们未来的一些工作将集中在叶毒力所需的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？我们还发现了一个高度保守的基因（YE0566），该基因可以激活psp基因表达并抑制psp零菌株的分泌素敏感性。该基因可能在细胞快速生长时指导53个氨基酸的细胞质膜蛋白的产生，或在细胞进入静止期时指导RpoS诱导的非编码RNA的产生。我们想了解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。为了实现我们的所有目标，我们建议：(1)研究诱导信号如何被Psp系统检测和转导；(2)分析PspB和PspC蛋白如何阻止分泌素通过细胞质膜；(3)探讨YE0566的调控和功能。这些研究除了小肠结肠炎耶氏菌外，还具有广泛的意义，因为对毒力至关重要的含分泌素系统、Psp系统和YE0566同源物在医学上重要的细菌中广泛存在。

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.