RovA regulon of Yersinia pestis

描述（由申请人提供）：鼠疫耶尔森氏菌是一种革兰氏阴性细菌人类病原体，是鼠疫的病原体。历史上Y。鼠疫是人类发病率和死亡率居高不下的原因。由于Y.鼠疫，它已成为生物战和生物恐怖主义的代理人。对Y.鼠疫将有助于确定疫苗开发和治疗的目标。目前，除了对III型分泌系统和毒力质粒上编码的效应子的研究外，对Y.分子水平上的鼠疫关于耶尔森氏菌的致病机理的大部分知识来自于对该属中另外两种人类病原体的研究，即耶尔森氏菌。enterocolitica和Y.假结核，这两种主要是肠道病原体，但能够引起全身感染，很像Y。鼠疫肠致病性耶尔森氏菌是一些最具特征的病原体，由于易于遗传操作和使用小鼠作为模型。鼠耶尔森氏菌病概括了人类疾病的大部分方面，允许详细分析发病机制。所有三种致病性耶尔森氏菌都具有完全毒力所需的毒力质粒。然而，使用Y.在小肠结肠炎中，我们采用了多种技术来鉴定染色体上编码的许多毒力因子。其中一个基因是马尔R家族的转录调节因子，称为rovA。RovA存在于耶尔森氏菌的所有致病性物种中，并且已被证明调节耶尔森氏菌中的许多毒力因子。小肠结肠炎RovA的沙门氏菌同源物还调节沙门氏菌中的几种毒力因子。虽然RovA和SlyA显然是毒力的调节因子，但调节的毒力因子并不相同，这表明RovA调节的基因可能因物种而异。这些观察结果使我们假设Y。RovA是鼠疫菌毒力调节因子，通过研究RovA在鼠疫菌毒力调节中的作用，证实了RovA在鼠疫菌毒力调节中的作用。我们将对鼠疫的发病机理有更深入的了解。具体而言，我们提出：（I）分析RovA在Y.（2）鼠疫菌的鉴定;鼠疫菌RovA调节基因产物;我们预测这些RovA调节基因中的一些将是鼠疫菌所特有的。pestis（与Y.小肠结肠炎菌或沙门氏菌）。

DESCRIPTION (provided by applicant): Yersinia pestis is a Gram-negative bacterial human pathogen that is the causative agent of plague. Historically Y. pestis has been responsible for significant human morbidity and mortality. Due to the high mortality rates and severe disease caused by Y. pestis, it has emerged as an agent of biological warfare and bioterrorism. A more detailed understanding of the pathogenesis of Y. pestis will facilitate the identification of targets for vaccine development and treatment. Currently, aside from studies of the type III secretion system and effectors encoded on the virulence plasmid, very little is known about the pathogenesis of Y. pestis at the molecular level. Much of what is known about the pathogenesis of Yersiniae comes from the investigation of the other two human pathogens in the genus, Y. enterocolitica and Y. pseudotuberculosis, both of which are primarily enteric pathogens but are capable of causing systemic infection much like Y. pestis. The enteropathogenic Yersiniae are some of the best-characterized pathogens due to the ease of genetic manipulation and the use of the mouse as a model. Murine yersiniosis recapitulates most aspects of disease in humans allowing for a detailed analysis of the pathogenesis. All three pathogenic species of Yersinia have virulence plasmids that are required for full virulence. However, using Y. enterocolitica we have employed a wide variety of techniques to identify numerous virulence factors that are encoded on the chromosome. One of these genes is a transcriptional regulator of the MarR family called rovA. RovA is present in all pathogenic species of Yersinia and has been demonstrated to regulate numerous virulence factors in Y. enterocolitica. The Salmonella homologue of RovA also regulates several virulence factors in Salmonella. Although RovA and SlyA are clearly regulators of virulence, the virulence factors regulated are not the same, suggesting that RovA regulated genes may differ depending on the species. Together these observations lead us to hypothesize that the Y. pestis RovA is a regulator of virulence and that by studying the role of RovA in the virulence of Y. pestis we will gain a greater understanding of the pathogenesis of plague. Specifically we propose: (I) Analysis of the role of RovA in the virulence of Y. pestis, and (2) Identification of the Y. pestis RovA regulated gene products; we predict some of these rovA regulated genes will be unique to Y. pestis (compared to Y. enterocolitica or Salmonella).