RNA helicases in bacterial pathogenesis

项目总结 细菌快速感知并对环境变化做出反应的能力是基本的 为殖民和生存干杯。转录后调控正在成为一项重要的战略， 促进对细菌毒力的有效和精确控制，从而在 发病机制。肠出血性大肠埃希菌O157：H7(EHEC)是一种 定植于人的结肠，并导致严重出血性结肠炎和溶血性尿毒症综合征 (HUS)，这可能是致命的。EHEC编码几个重要的毒力因子，包括强大的 引起HUS的志贺毒素和3型分泌系统(T3SS)以及 附着和消除(AE)对肠细胞的损伤形成。EHEC的感染量非常低， 提示EHEC已进化出时空调控毒力基因的机制 表达式出现在适当的宿主小生境中。RNA解旋酶在世界上所有王国中普遍存在。 生命，以及在病毒基因组中，并参与几乎所有方面的RNA新陈代谢， 包括RNA的降解或保护和翻译。我们的研究强调了RNA的重要性 解旋酶对EHEC生态位的适应和毒力基因表达的协调。建议数 研究工作将调查RNA解旋酶对生态位识别和寄主病原体的重要性 使用生理上相关的感染模型进行交互。我们还将利用公正的方法 全面绘制肠出血性大肠杆菌解旋酶的调控图，并确定调控靶点。

PROJECT SUMMARY The ability of bacteria to rapidly sense and respond to changes in the environment is fundamental to colonization and survival. Post-transcriptional regulation is emerging as an important strategy that promotes efficient and precise control of bacterial virulence, and thus plays a central role in pathogenesis. Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a bacterial pathogen that colonizes the human colon and causes severe hemorrhagic colitis and hemolytic uremic syndrome (HUS), which can be fatal. EHEC encodes several important virulence factors, including the potent Shiga toxin that causes HUS and a type three secretion system (T3SS) and effectors necessary for attaching and effacing (AE) lesion formation on enterocytes. EHEC has a very low infectious dose, suggesting that EHEC has evolved mechanisms to spatiotemporally control virulence gene expression to occur within appropriate host niches. RNA helicases are ubiquitous in all kingdoms of life, as well as within viral genomes, and are involved in virtually all aspects of RNA metabolism, including RNA degradation or protection and translation. Our studies underlie the importance of RNA helicases to EHEC niche adaptation and coordination of virulence gene expression. The proposed work will investigate the importance of RNA helicases to niche recognition and host-pathogen interactions using a physiologically relevant infection model. We will also utilize unbiased approaches to comprehensively map the regulon of an EHEC helicase and identify targets of regulation.