The Psp response of Yersinia enterocolitica

小肠结肠炎耶尔森氏菌的 Psp 反应

• 批准号: 6717703
• 负责人: ANDREW J. DARWIN
• 金额: $ 27.04万
• 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 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6717703
• 关键词: DNA binding protein; Yersinia; bacterial genetics; biological signal transduction; gene induction /repression; gene mutation; host organism interaction; laboratory mouse; virulence

DESCRIPTION (provided by applicant): Bacteria of the genus Yersinia are responsible for a variety of human diseases. Y. pestis causes Bubonic Plague, and has recently regained prominence in public awareness due to its potential use as an agent of bioterrorism. In contrast, Y. pseudotuberculosis and Y. enterocolitica cause primarily gastrointestinal disease. However, despite the differences in disease symptoms, the three 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 III secretion system (TTSS). In Yersinia, as in all bacterial pathogens, many of the proteins that play important roles in virulence, including components of the TTSS, are located in the cell envelope. Under certain conditions, some envelope proteins become misfolded/mislocalized. Specific stress-response mechanisms deal with this problem, examples of which are the RpoE and Cpx systems of Escherichia coli and related organisms. These extracytoplasmic stress responses play important roles during host infection. The central hypothesis of this proposal is that a different extracytoplasmic stress response system is encoded by the phage-shock-protein locus (psp) of Y. enterocolitica. A Y. enterocolitica psp mutant is avirulent, and homologus psp loci are found in other bacterial pathogens, including Y. pestis and Vibrio cholerae. Our preliminary data indicate that the Psp system responds to mislocalization of several envelope proteins involved in virulence, including at least one component of a TTSS. By studying the Psp system we will gain further insight into the essential ability of bacteria to respond to stressful conditions that occur during host infection. Specifically, we propose to: (1) Analyze the proteins that induce the Psp system and characterize any overlap between Psp inducers and RpoE/Cpx inducers; (2) Determine the topology of the Psp system, and investigate how Psp allows extracytoplasmic stress to be sensed and signaled across the cytoplasmic membrane; (3) Characterize genes directly controlled by the Psp system, in order to identify further stress response components.

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腺鼠疫，由于其可能被用作生物恐怖主义的媒介，最近在公众意识中重新获得了关注。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，但这三种致病性耶尔森氏菌密切相关，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，包括广泛的 III 型分泌系统 (TTSS) 的第一个例子。在耶尔森氏菌中，与所有细菌病原体一样，许多在毒力中发挥重要作用的蛋白质（包括 TTSS 的成分）都位于细胞包膜中。在某些条件下，一些包膜蛋白会错误折叠/错误定位。特定的应激反应机制可以解决这个问题，例如大肠杆菌和相关生物体的 RpoE 和 Cpx 系统。这些胞质外应激反应在宿主感染过程中发挥着重要作用。该提议的中心假设是，小肠结肠炎耶尔森氏菌的噬菌体休克蛋白基因座（psp）编码不同的胞质外应激反应系统。 小肠结肠炎耶尔森氏菌 psp 突变体是无毒的，在其他细菌病原体中也发现了同源 psp 位点，包括鼠疫耶尔森氏菌和霍乱弧菌。我们的初步数据表明，Psp 系统对与毒力有关的几种包膜蛋白的错误定位做出反应，其中至少包括 TTSS 的一种成分。通过研究 Psp 系统，我们将进一步了解细菌对宿主感染期间发生的应激条件做出反应的基本能力。具体来说，我们建议：（1）分析诱导 Psp 系统的蛋白质，并表征 Psp 诱导剂和 RpoE/Cpx 诱导剂之间的任何重叠； (2) 确定Psp系统的拓扑结构，并研究Psp如何让胞质外应激通过细胞质膜被感知并发出信号； (3)表征由Psp系统直接控制的基因，以识别进一步的应激反应成分。