The Psp response of Yersinia enterocolitica

耶尔森氏菌属细菌是导致人类多种疾病的原因。鼠疫杆菌导致臭名昭著的 疾病瘟疫，由于其作为一种潜在的病原体而在公众意识中重新引起注意 生物恐怖主义。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，这三种致病耶尔森氏菌却是密切相关的 相关，并有几个共同的毒力决定因素。耶尔西尼亚菌的研究提供了基本的 对细菌发病机制的洞察，包括第一例广为流传的3型分泌系统 (T3SS)。所有T3SS的关键成分是一种特殊的外膜成孔蛋白，称为 分泌素。然而，分泌素的产生会导致细菌细胞被膜应激。这对Y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系统对其毒力是必不可少的。我们对PSP系统的研究 DATE已经确定了其核心组成部分，并开始确定其作用。我们未来的工作将建立在 假设小肠结肠炎耶尔森菌PSP系统的调节是由复杂的动态蛋白介导的 交互，并且激活的系统起作用以应对与 细胞质膜等可引起分泌素的错位。为了解决这些假设，我们 提出：(1)检验PspF、PSPA、PSPB和PSPC蛋白构成信号转导的模型 通过蛋白质之间的相互作用和PSPA或PspF的变化来调节PSP基因表达的系统 (2)分析PSPB和PSPC蛋白的调节和生理功能， 它们在系统中扮演多种重要角色；(3)直接分析分泌素毒性、 小肠结肠炎耶尔森氏菌分泌素在细胞膜上的错误定位以及PSP系统的功能。 这些研究在小肠结肠炎耶尔森菌之外也具有广泛的意义，因为含有分泌素的系统 对毒力至关重要的，以及PSP系统，在医学上重要的细菌中广泛存在。因此，通过 了解PSP系统，我们将进一步深入了解细菌对 在宿主感染期间发生的应激状态。

Bacteria of the genus Yersinia are responsible for a variety of human diseases. Y. pestis causes the infamous disease Plague, which has 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, these 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 three secretion system (T3SS). A critical component of all T3SSs is a specialized 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 its virulence. Our studies on the Psp system to date have identified its core components and begun to define their roles. We will base our future work on the hypotheses that regulation of the Y. enterocolitica Psp system is mediated by complex and dynamic proteinprotein interactions, and that the activated system functions to counter problems associated with the cytoplasmic membrane, such as can be caused by a mislocalized secretin. To address these hypotheses we propose to: (1) Test the model that PspF, PspA, PspB and PspC proteins constitute a signal transduction system that regulates psp gene expression via protein-protein interactions and changes in PspA or PspF subcellular location; (2) Analyze the regulatory and physiological functions of the PspB and PspC proteins, which play multiple essential roles in the system; (3) Directly analyze the connections between secretin toxicity, secretin mislocalization to the cytoplasmic membrane, and the function of the Psp system in Y. enterocolitica. These studies also have broad significance beyond Y. enterocolitica because secretin-containing systems critical for virulence, and the Psp system, are widespread in medically important bacteria. Therefore, by understanding the Psp system we will gain further insight into the essential ability of bacteria to respond to stressful conditions that occur during host infection.