Genetic and Ecological Factors in Transmissibility and Epidemic Cycle of Cholera

霍乱传播性和流行周期的遗传和生态因素

基本信息

批准号：
7902138
负责人：
John Joseph Mekalanos
金额：
$ 32.2万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7902138
关键词：
Acute Adult Aliquot Animal Model Antibiotic Resistance Antibodies Area Bacteria Bacteriophages Bangladesh Biochemical Biochemical Genetics Cells Characteristics Cholera Data Developing Countries Development Disease Environment Environmental Monitoring Epidemic Excretory function Exhibits Feces Fresh Water Genes Genetic Genomics Growth Human Intestines Ionic Strengths Ions Kinetics L Cells Laboratories Libraries Liquid substance Lytic Metabolic Metabolic stress Methods Microbial Biofilms Modeling Molecular Profiling Monitor Morphology Nature Nutrient Organism Oryctolagus cuniculus Other Genetics Patients Population Predatory Behavior Prevalence Process Property Publishing Reagent Research Design Research Personnel Resistance Resuscitation Role Screening procedure Seasons Sodium Specificity Stress Surface Swimming System Techniques Temperature Testing Vibrio Vibrio cholerae Virulence Virulent Water base biological adaptation to stress cell injury cell type deprivation disease natural history effective intervention in vivo mutant particle pathogen physical property programs sodium ion transmission process water sampling waterborne

Acute Adult Aliquot Animal Model Antibiotic Resistance Antibodies Area Bacteria Bacteriophages Bangladesh Biochemical Biochemical Genetics Cells Characteristics Cholera Data Developing Countries Development Disease Environment Environmental Monitoring Epidemic Excretory function Exhibits Feces Fresh Water Genes Genetic Genomics Growth Human Intestines Ionic Strengths Ions Kinetics L Cells Laboratories Libraries Liquid substance Lytic Metabolic Metabolic stress Methods Microbial Biofilms Modeling Molecular Profiling Monitor Morphology Nature Nutrient Organism Oryctolagus cuniculus Other Genetics Patients Population Predatory Behavior Prevalence Process Property Publishing Reagent Research Design Research Personnel Resistance Resuscitation Role Screening procedure Seasons Sodium Specificity Stress Surface Swimming System Techniques Temperature Testing Vibrio Vibrio cholerae Virulence Virulent Water base biological adaptation to stress cell injury cell type deprivation disease natural history effective intervention in vivo mutant particle pathogen physical property programs sodium ion transmission process water sampling waterborne

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项目摘要

DESCRIPTION (provided by applicant): Toxigenic Vibrio cholerae belonging to the O1 and O139 serogroups cause cholera, an acute, waterborne diarrheal disease that causes seasonal epidemics in many developing countries such as Bangladesh. Although transmission of cholera typically occurs through water contaminated with the pathogenic organisms, the natural mechanisms that facilitate the epidemic spread of cholera and support the survival of the pathogen in water between seasonal epidemics in Bangladesh are not clear. We will apply a new method we developed called AST to monitor and study the nature of "conditionally viable environmental cells (CVEC)" of pathogenic V. cholerae that exist in surface waters of Bangladesh. Because CVEC are likely derived from biofilm-like aggregates of V. cholerae shed in human cholera stools, we propose a broad program to understand the infectious form of V. cholerae in cholera stools, and their survival in the aquatic environment. We will isolate CVEC from environmental waters and characterize them metabolically, morphologically, immunochemically, and for their innate infectivity in animal models. Because we have shown phage predation apparently ends cholera epidemics, we will determine whether CVEC of V. cholerae are protected from phage predation due to their possible low metabolic activity or physical properties. Our proposed analysis will include biochemical and genetic studies designed to understand enhanced transmissibility of stool-derived vibrios, their environmental survival as CVEC and resuscitation of CVEC to pathogenic viable organisms. We propose to produce CVEC-like V. cholerae cells from cholera stools (CVEC-H), or from cells shed by experimentally infected rabbits (CVEC-R) or under fully laboratory conditions (CVEC-L). To understand the genetic basis for the transition between various cell types, we will conduct microarray-based, genomic transcriptional analysis. Standard genetic methods will be utilized to identify genes involved in formation of CVEC-R and CVEC-L. A library of 2623 defined transposon insertion mutants of V. cholerae will aid in the systematic identification of genes involved in low sodium osmo-stress. Together with data from environmental monitoring, these studies should provide a better understanding of the infectious cycle of cholera and thus inspire new effective interventions for interrupting the natural history of this disease in developing countries.

描述（由申请人提供）：属于O1和O139血清群的毒蛇霍乱引起霍乱，这是一种急性，水性腹泻病，在孟加拉国等许多发展中国家引起季节性流行病。尽管霍乱的传播通常是通过被致病生物污染的水发生的，但促进霍乱流行并支持孟加拉国季节性流行病之间的病原体生存的自然机制尚不清楚。我们将应用一种我们开发的称为AST的新方法来监测和研究孟加拉国地表水中存在的致病性V.霍乱的“有条件可行的环境细胞（CVEC）”的性质。由于CVEC可能是从人类霍乱凳子中的V.霍乱棚的生物膜样骨料中得出的，因此我们提出了一个广泛的程序，以了解霍乱粪便中V.霍乱的传染性形式，以及它们在水生环境中的生存。我们将与环境水域分离CVEC，并以形式，形态，免疫化学以及它们在动物模型中的先天感染性上的代谢表征。由于我们已经显示出噬菌体捕食显然结束了霍乱流行病，因此我们将确定霍乱弧菌的CVEC是否由于其可能的低代谢活性或物理特性而受到噬菌体捕食的保护。我们提出的分析将包括旨在了解粪便衍生的颤音的可传播性的生化和遗传研究，它们作为CVEC的环境生存以及CVEC复苏到致病性可行生物体。我们建议从霍乱粪便（CVEC-H）或通过实验感染的兔子（CVEC-R）或在完全实验室条件（CVEC-L）中产生类似CVEC的V.霍乱细胞。为了了解各种细胞类型之间过渡的遗传基础，我们将进行基于微阵列的基因组转录分析。标准遗传方法将用于鉴定与CVEC-R和CVEC-L形成有关的基因。 2623个定义的霍乱弧菌插座插入突变体的库将有助于系统地识别涉及低钠OSMO压力的基因。与环境监测的数据一起，这些研究应更好地了解霍乱的传染性周期，从而激发新的有效干预措施，以中断发展中国家这种疾病的自然历史。