YsrRS regulon of Y. enterocolitica

描述（由申请人提供）：小肠结肠炎耶尔森氏菌是耶尔森氏菌属的三种致病菌之一。它引起的疾病症状从轻度胃肠炎到全身感染，通常是致命的。感染的症状和进展在小鼠模型中重现，使其不仅成为重要的病原体，而且成为研究毒力的极好模型系统。致病性耶尔森氏菌毒力的一个主要组成部分是一个大的质粒，它编码一个完整的三型分泌系统（Ysc TTSS），包括装置，易位，和效应。近年来，在耶尔森氏菌上发现了耶尔森氏菌分泌器（Yersinia secretion apparatus，TTSS）。小肠结肠炎菌染色体和牵连作为毒力决定因素。在Y染色体上未发现ysa位点。鼠疫菌或Y.假结核，也没有在非或低致病性Y。小肠结肠炎菌株。Ysa TTSS与沙门氏菌的SPI-1 TTSS和志贺氏菌的Mxi-Spa TTSS的关系最为密切。因此，像肠道沙门氏菌一样，它有两个TTSS，在感染过程中发挥不同的作用，Ysc和Ysa TTSS可能对Y.小肠结肠炎与广泛研究的Ysc系统相比，对Ysa TTSS知之甚少。至少八种Ysp（耶尔森氏菌分泌蛋白）通过Ysa TTSS分泌，并且仅在2000年观察到体外分泌。 26 ℃，在具有高NaCl浓度的L-肉汤中。据信编码该装置的基因簇的近端是两个与双组分调控系统YsrRS同源的基因。本实验室的最新研究结果表明，YsrRS在高盐胁迫下调控ysa的表达中起重要作用。该提案的总体目标是更好地表征Ysa TTSS在毒力中的作用，并更好地了解YsrRS对其的调节。我们工作的目标是检验以下假设：（a）Ysa TTSS在感染的早期步骤中起作用，（B）YsrRS是Ysa系统响应NaCl和可能响应其他条件的重要调节因子，以及（c）YsrRS调节其他基因，其中一些可能在毒力中起作用。

DESCRIPTION (provided by applicant): Yersinia enterocolitica is one of three pathogenic species of the genus Yersinia. It is responsible for disease symptoms ranging from a mild gastroenteritis to systemic infection, which is often fatal. The symptoms and progression of infection are recapitulated in a mouse model, making this not only an important pathogen but also an excellent model system for studying virulence. A major component in the virulence of pathogenic Yersinia is a large plasmid that encodes a complete type three secretion system (the Ysc TTSS) including the apparatus, translocators, and effectors. Recently, the Ysa (Yersinia secretion apparatus) TTSS was discovered on the Y. enterocolitica chromosome and implicated as a virulence determinant. The ysa locus is not found in Y. pestis or Y. pseudotuberculosis, nor in non- or low-pathogenic Y. enterocolitica strains. The Ysa TTSS is most closely related to the SPI-1 TTSS of Salmonella and Mxi-Spa TTSS of Shigella. Thus, like Salmonella enterica, which has two TTSS that play different roles during the infectious process, the Ysc and Ysa TTSS may play distinct roles for Y. enterocolitica. Compared to the extensively studied Ysc system, little is known about the Ysa TTSS. At least eight Ysp's (Yersinia secreted proteins) are secreted through the Ysa TTSS, and in vitro secretion has only been observed at 26 degrees C in L-broth with high NaC1 concentrations. Proximal to the duster of genes believed to encode the apparatus are two genes with homology to a two-component regulatory system, YsrRS. Recent results from our laboratory indicated that YsrRS are important in regulating expression of ysa in response to high salt. The overall aims of this proposal are to better characterize the role of the Ysa TTSS in virulence and to better understand its regulation by YsrRS. The goals of our work are to test the hypotheses that (a) the Ysa TTSS plays a role in the early steps of infection, (b) YsrRS are important regulators of the Ysa system in response to NaC1 and possibly in response to other conditions, and (c) YsrRS regulate additional genes, some of which may play a role in virulence.