Environmental adaptation by Vibrio cholerae

霍乱弧菌的环境适应

基本信息

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
项目类别：
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

项目摘要

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病，每年影响3-5万人。霍乱是由弧菌霍乱引起；革兰氏阴性细菌和辅助人类病原体，原生世界各地的水生生态系统。 V.霍乱的全球分布使其成为重要的健康威胁每次人口都无法获得清洁水和良好的卫生设施；事实海地和也门正在进行的霍乱流行病的例证。毁灭性的后果霍乱结合了它可以传播的速度，不断发展的抗生素耐药性及其能力持续存在于水生生态系统中，强调了开发新方法的需求限制这种流行病的传播。我们最近发现产生的细胞代谢产物作者：霍乱V.可以用作下调毒力因子产生的环境线索霍乱毒素和毒素核心菌毛。在此提案中，我们将研究细胞代谢产物和其他环境信号调节V.霍乱生命中涉及的转录响应循环。提出了两个具体目标。第一个目标将表征LYSR家庭的作用霍乱发病机理和环境适应的转录调节剂leuo。第二个 AIM将研究膜结合的转录调节剂TOXR感官并响应环境刺激。确定调节的调节机制和环境线索自适应反应将阐明V.霍乱发病机理的重要方面，提供更好的了解导致流行病的因素，并可能导致发展抗击霍乱的新型方法。