RNA helicases in bacterial pathogenesis

项目摘要 细菌快速感知和响应环境变化的能力是根本 殖民和生存的关键转录后调控正成为一种重要的策略， 促进细菌毒力的有效和精确控制，因此在以下方面发挥核心作用： 发病机制肠出血性大肠杆菌O 157：H7（EHEC）是一种细菌病原体， 定植于人类结肠并引起严重的出血性结肠炎和溶血性尿毒综合征 (HUS)，这可能是致命的。肠出血性大肠杆菌编码几种重要的毒力因子，包括强毒力因子。 导致HUS的滋贺毒素和三型分泌系统（T3 SS）以及 肠上皮细胞上的附着和消失（AE）损伤形成。肠出血性大肠杆菌的感染剂量非常低， 提示肠出血性大肠杆菌已进化出时空控制毒力基因的机制 表达发生在适当的宿主生态位内。RNA解旋酶普遍存在于所有生物界中。 生命，以及病毒基因组内，并参与RNA代谢的几乎所有方面， 包括RNA降解或保护和翻译。我们的研究强调了RNA的重要性 解旋酶对肠出血性大肠杆菌生态位适应和毒力基因表达的协调作用。拟议 研究RNA解旋酶在生态位识别和宿主-病原体关系中的重要性 使用生理相关的感染模型的相互作用。我们还将利用无偏见的方法 全面绘制肠出血性大肠杆菌解旋酶的调节子并确定调节靶点。

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.