Environmental adaptation by Vibrio cholerae

项目概要/摘要 霍乱是一种急性肠道疾病，每年影响300万至500万人。霍乱是 由霍乱弧菌引起;一种革兰氏阴性细菌和兼性人类病原体， 世界各地的水生生态系统霍乱弧菌的全球分布使其成为一种重要的 任何时候人类无法获得清洁水和良好的卫生设施都会造成健康威胁;这是一个事实 海地和也门正在发生的霍乱疫情就是例证。的破坏性后果 霍乱与它传播的速度，进化的抗生素耐药性，以及它的能力相结合， 在水生生态系统中持续存在，强调了开发新方法的必要性 来限制这种流行病的传播我们最近发现细胞代谢产物 可以作为环境线索下调毒力因子的产生 霍乱毒素和毒素共调节菌毛。在这个提议中，我们将研究细胞代谢物如何 和其他环境信号调节参与霍乱弧菌生命的转录反应 周期提出了两个具体目标。第一个目标将描述LysR家族的作用 转录调节因子LeuO在霍乱弧菌发病机制和环境适应中的作用。第二 目的是研究膜结合转录调节因子ToxR如何感知和响应 环境刺激确定调节机制和环境线索， 适应性反应将阐明霍乱弧菌发病机制的重要方面， 了解有助于流行病传播的因素，并可能导致发展 新的方法来对抗霍乱

PROJECT SUMMARY/ABSTRACT Cholera is an acute diarrheal disease that affects 3-5 million people each year. Cholera is caused by Vibrio cholerae; a Gram-negative bacterium and facultative human pathogen that is native to aquatic ecosystems around the world. The worldwide distribution of V. cholerae makes it a significant health threat anytime human populations lack access to clean water and good sanitation; a fact exemplified by the ongoing cholera epidemics in Haiti and Yemen. The devastating consequences of cholera combined with the rapidity with which it can spread, evolving antibiotic resistance, and its ability to persist in aquatic ecosystems, have underscored the need for the development of novel approaches to limit the spread of this epidemic disease. We recently discovered that cellular metabolites produced by V. cholerae can serve as environmental cues to downregulate the production of the virulence factors cholera toxin and the toxin coregulated pilus. In this proposal, we will investigate how cell metabolites and other environmental signals modulate transcriptional responses involved in the V. cholerae life cycle. Two specific aims are proposed. The first aim will characterize the role of the LysR-family transcriptional regulator LeuO in V. cholerae pathogenesis and environmental adaptation. The second aim will investigate how the membrane-bound transcriptional regulator ToxR senses and responds to environmental stimuli. Determining the regulatory mechanisms and environmental cues that modulate adaptive responses will illuminate important aspects of V. cholerae pathogenesis, provide a better understanding of the factors that contribute to the epidemic spread, and may lead to the development of novel approaches to combat the disease cholera.