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: 7491510
• 负责人: John Joseph Mekalanos
• 金额: $ 29.41万
• 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/7491510
• 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）：我们提出了一系列研究，以了解细菌病毒（颤音或噬菌体）在霍乱流行病学和弧菌霍乱的演变中的作用。我们还希望理解霍乱特有区域中自然水生环境的各个方面，这些地区影响噬菌体介导的和非洁变的介导的事件，这些事件对霍乱具有生物学意义。来自孟加拉国环境场所的颤音噬细胞将被隔离和表征。基因组微阵列将用于确定它们是否具有潜在的毒力基因。将与霍乱基因组DMA杂交的噬菌体基因组进行测序，以了解其进化起源。我们将识别并表征由洛杉矶弧菌在霍乱弧菌上生长产生的生物学活性分子，这些分子对已知的毒素和信号分子而言为阴性。我们还将确定噬菌体在适当的霍乱动物模型中是否影响V.霍乱的传染剂量。我们将测试这个理论，即TLC是一种卫星噬菌体，它带有毒素编码CTX噬菌体的附着位点。通过寻找重组热点，例如晶体成分和染色体岛，将研究DNA转化的作用。我们还将尝试确定影响变化效率或噬菌体霍乱的噬菌体的因素。我们将扩大周围环境水的既定档案，并研究水影响霍乱弧菌生物学特性的能力的变化，例如生物膜形成，多层细胞的产生和噬菌体的稳定性。将监测水的非纤维状物种，该物种是颤音的替代宿主。这样的宿主将针对环境监视，以评估其作为促进颤音噬菌体“盛开”在水生环境中的潜在作用，这反过来又对噬菌体敏感的流行病V.霍乱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指标，因此有助于通过各种干预措施控制这种致命疾病。