YsrRS regulon of Y. enterocolitica

描述(申请人提供)：小肠结肠炎耶尔森氏菌是耶尔森氏菌属的三个致病种之一。它导致从轻度胃肠炎到系统性感染等各种疾病症状，后者往往是致命的。感染的症状和进展在小鼠模型中被概括，这使得这不仅是一个重要的病原体，而且是研究毒力的一个很好的模型系统。致病性耶尔森氏菌毒力的主要成分是编码完整的3型分泌系统(YSC TTSS)的一个大质粒，包括器官、转运子和效应器。最近，耶尔森氏菌分泌器(Ysa)TTSS在小肠结肠炎耶尔森氏菌染色体上被发现，并被认为是毒力决定因素。在鼠疫耶尔森氏菌或假结核耶尔森菌中未发现ysa基因座，在非致病性或低致病性的小肠结肠炎耶尔森菌中也未发现ysa基因座。Ysa TTSS与沙门氏菌的SPI-1 TTSS和志贺氏菌的MXI-Spa TTSS关系最为密切。因此，与肠炎沙门氏菌一样，YSC和Ysa TTS在感染过程中扮演着不同的角色，可能对小肠结肠炎耶尔森菌具有不同的作用。与被广泛研究的YSC系统相比，人们对YSA TTSS知之甚少。至少有8个YSP(耶尔森氏菌分泌蛋白)通过YSa TTSS分泌，并且只有在26℃的高浓度NaCl2的L发酵液中才能观察到体外分泌。在据信编码该装置的基因的最近端有两个基因，它们与一个双组分调控系统YsrRS同源。我们实验室的最新结果表明，YsrRs在调节ysa在高盐胁迫下的表达方面起着重要的作用。这项建议的总体目标是更好地描述Ysa TTSS在毒力中的作用，并更好地了解YsrRs对其的调控。我们工作的目的是检验以下假设：(A)YsA TTSS在感染的早期步骤中发挥作用，(B)YsrRs是Ysa系统对NaC1以及可能对其他条件的反应的重要调节因子，以及(C)YsrRs调节额外的基因，其中一些基因可能在毒力中发挥作用。

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.