Phages and Genomic Variation in Vibrio Cholerae Evolution

霍乱弧菌进化中的噬菌体和基因组变异

• 批准号: 7319534
• 负责人: John Joseph Mekalanos
• 金额: $ 31.14万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7319534
• 关键词: Animal Model; Archives; Area; Bacteria; Bacteriophage Typing; Bacteriophages; Bangladesh; Biological; Cells; Chitin; Cholera; Cholera Toxin; Chromosomes; Collection; Competence; Cyclophosphamide; Cytotoxin; DNA; Disease; Dose; Elements; Engineering; Enteral; Enterotoxins; Environment; Epidemic; Epidemiology; Essential Genes; Event; Evolution; Family; Feces; Functional disorder; Funding; Future; Generations; Genes; Genetic; Genetic Transformation; Genome; Genomics; Growth; Horizontal Gene Transfer; Hot Spot; Human; In Vitro; Infection; Intervention; Investigation; Island; Kinetics; Laboratories; Lytic; Mediating; Medical Surveillance; Microbial Biofilms; Modeling; Monitor; Mozambique; Oryctolagus cuniculus; Patients; Pattern; Phylogenetic Analysis; Play; Prevalence; Principal Investigator; Production; Property; Prophages; Publishing; Range; Relative (related person); Reporting; Research Personnel; Resistance; Resources; Role; Sampling; Seasons; Series; Serotyping; Signal Transduction; Signaling Molecule; Site; Testing; Time; Toxin; Variant; Vibrio; Vibrio cholerae; Vibrio cholerae O1; Vibrio cholerae non-O1; Virulence; Water; base; fitness; in vivo; interest; killings; mutant; novel; pandemic disease; progenitor; programs; theories; tissue culture; transmission process; uptake; water sampling

DESCRIPTION (provided by applicant): We propose a series of studies to understand the role of bacterial viruses (vibriophage or phage) in cholera epidemiology and the evolution of Vibrio cholerae. We also hope to understand the aspects of the natural aquatic environment in a cholera endemic area that influence phage-mediated and non-phage mediated events that have biological significance to cholera. Vibriophages from Bangladesh environmental sites will be isolated and characterized. Genomic microarrays will be used to determine if they carry potential virulence genes. Phage genomes that hybridize with V. cholerae genomic DMA will be sequenced to understand their evolutionary origins. We will identify and characterize biologically active molecules produced by the growth of lytic vibriophages on V. cholerae engineered to be negative for known toxins and signaling molecules. We also will determine if phages influence the infectious dose of V. cholerae in appropriate animal models for cholera. We will test this theory that TLC is a satellite phage that carries the attachment site for the toxin- encoding CTX phage. The role of DNA transformation will be studied by looking for recombinational hot spots such as the superintegron and chromosomal islands. We will also attempt to identify factors in water that influence transformation efficiency or phage killing of V. cholerae. We will expand an established bi- weekly archive of environmental water and study variations in the water's ability to influence biological properties of V. cholerae such as biofilm formation, generation of domant cells, and stability of phages. Water will be monitored for a non-Vibrio species that acts as an alternative host for vibriophages. Such a host will be targeted for environmental surveillance in order to assess its potential role as a co-factor in promoting vibriophage "blooms" within aquatic environments which in turn should have a deleterious effect on the concentration of phage sensitive epidemic V. cholerae strains. The seasonal fluctuation of the parameters we selected may be strong predictors of cholera seasonality in Bangladesh and thus aid in the control of this deadly disease by a variety of interventions.

描述(由申请人提供)：我们建议进行一系列研究，以了解细菌病毒(噬菌体或噬菌体)在霍乱流行病学中的作用和霍乱弧菌的进化。我们还希望了解霍乱流行地区的自然水环境对霍乱具有生物学意义的噬菌体介导和非噬菌体介导的事件的影响。来自孟加拉国环境地点的噬弧菌将被分离和鉴定。基因组微阵列将用于确定它们是否携带潜在的毒力基因。与霍乱弧菌基因组DNA杂交的噬菌体基因组将被测序，以了解它们的进化起源。我们将鉴定和表征霍乱弧菌裂解噬菌体生长产生的生物活性分子，这些霍乱弧菌经改造后对已知毒素和信号分子呈阴性反应。我们还将确定在适当的霍乱动物模型中，噬菌体是否会影响霍乱弧菌的感染量。我们将测试这一理论，即TLC是一个卫星噬菌体，携带毒素编码的CTX噬菌体的附着位点。DNA转化的作用将通过寻找重组热点来研究，如超级整合子和染色体岛。我们还将尝试确定水中影响霍乱弧菌转化效率或噬菌体杀灭的因素。我们将扩大已建立的双周环境水档案，并研究水影响霍乱弧菌生物特性的能力的变化，如生物膜形成、优势细胞的生成和噬菌体的稳定性。将监测水中是否有作为噬弧菌替代宿主的非弧菌物种。这种宿主将被作为环境监测的目标，以评估其作为促进水环境中噬菌体“大量繁殖”的辅助因素的潜在作用，这反过来又应该对对噬菌体敏感的流行霍乱弧菌菌株的浓度产生有害影响。我们选择的参数的季节性波动可能是孟加拉国霍乱季节性的有力预测因素，因此有助于通过各种干预措施控制这一致命疾病。