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性物种之一。它引起的疾病症状从轻微的肠胃炎到全身感染，通常是致命的。在小鼠模型中重现了感染的症状和进展，使其不仅是一种重要的病原体，而且是研究毒力的良好模型系统。致病性耶尔森菌毒力的一个主要组成部分是一个大的质粒，它编码完整的第三型分泌系统（Ysc TTSS），包括装置、易位子和效应器。最近，在小肠结肠炎耶尔森氏菌染色体上发现了Ysa（耶尔森氏菌分泌装置）TTSS，并与毒力决定因素有关。在鼠疫耶尔森菌或假结核耶尔森菌中没有发现ysa位点，在非致病性或低致病性小肠结肠炎耶尔森菌株中也没有发现。Ysa型TTSS与沙门氏菌的SPI-1型TTSS和志贺菌的Mxi-Spa型TTSS关系最为密切。因此，就像肠炎沙门氏菌有两个TTSS在感染过程中发挥不同的作用一样，Ysc和Ysa TTSS可能在小肠结肠炎沙门氏菌中发挥不同的作用。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种Ysp（耶尔森氏菌分泌蛋白）通过Ysa TTSS分泌，并且仅在26℃高NaC1浓度的l -肉汤中观察到体外分泌。据信编码该装置的基因簇的近端是与双组分调控系统YsrRS同源的两个基因。我们实验室最近的研究结果表明，YsrRS在高盐反应中调控ysa的表达是重要的。本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对其的调控。我们的工作目标是验证以下假设：(a) Ysa TTSS在感染的早期阶段发挥作用，(b) YsrRS是Ysa系统响应NaC1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，其中一些基因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.