Environmental adaptation by Vibrio cholerae

霍乱弧菌的环境适应

• 批准号: 9975688
• 负责人: JAMES Edward BINA
• 金额: $ 37.6万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-03 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975688
• 关键词: Acute Diarrhea; Address; Affect; Amino Acids; Antibiotic Resistance; Cell Density; Cells; Cholera; Cholera Toxin; Cues; DNA Binding Domain; Development; Diarrhea; Disease; Down-Regulation; Ecosystem; Environment; Epidemic; Family; Gene Expression; Genes; Genetic Transcription; Gram-Negative Bacteria; Haiti; Health; Human; Infection; Ingestion; Intestines; Lead; Life Cycle Stages; Mediating; Membrane; Metabolic; Metabolism; Metabolite Interaction; Oral; Pathogenesis; Phase; Phenotype; Pilum; Population; Production; Regulon; Research; Role; Sanitation; Signal Transduction; Stimulus; System; Testing; Time; Toxin; Vibrio cholerae; Vibrio cholerae stN protein; Virulence; Virulence Factors; Water; Yemen; aquatic organism; base; combat; diarrheal disease; environmental adaptation; extracellular; human pathogen; in vivo; novel; novel strategies; novel therapeutic intervention; periplasm; programs; purge; response; sensor; stem; transcription factor; transcriptome; transmission process

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.

项目摘要/摘要 霍乱是一种急性腹泻疾病，每年影响300-500万人。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，原产于 世界各地的水生生态系统。霍乱弧菌在世界范围内的分布使其成为一个重要的 当人类缺乏清洁的水和良好的卫生设施时，任何时候都会威胁健康；这是一个事实 海地和也门正在发生的霍乱疫情就是例证。造成的毁灭性后果 霍乱与它传播的速度结合在一起，进化出抗生素耐药性，以及它的能力 坚持水生生态系统，强调了开发新方法的必要性 以限制这种流行病的传播。我们最近发现，细胞代谢物产生 霍乱弧菌可以作为环境信号，下调毒力因子的产生。 霍乱毒素和共调节菌毛毒素。在这项提案中，我们将研究细胞代谢物是如何 和其他环境信号调节霍乱弧菌生命中涉及的转录反应 周而复始。提出了两个具体目标。第一个目标将描述LysR家族的角色 转录调控因子LeuO在霍乱弧菌致病和环境适应中的作用。第二 AIM将研究膜结合的转录调控因子ToxR是如何感知和反应的 环境刺激。确定调节的调节机制和环境线索 适应性反应将阐明霍乱弧菌致病机制的重要方面，提供更好的 了解导致疫情传播并可能导致发展的因素 与霍乱作斗争的新方法。