Theoretical and Experimental Studies of the Population and Evolutionary Dynamics of Bacteria and Bacteriophage.

细菌和噬菌体的种群和进化动力学的理论和实验研究。

• 批准号: 10331074
• 负责人: Bruce Richard Levin
• 金额: $ 39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10331074
• 关键词: Address; Archaea; Bacteria; Bacterial Infections; Bacteriophages; Basic Science; Biology; Biotechnology; Clustered Regularly Interspaced Short Palindromic Repeats; Computer Simulation; Development; Disease Outbreaks; Domestic Animals; Ecology; Escherichia coli; Evolution; Genetic; Human; Investigation; Lead; Liquid substance; Lytic; Maintenance; Mathematics; Mediating; Modeling; Molecular Biology; Natural Selections; Organism; Planet Earth; Play; Population; Population Biology; Population Study; Program Evaluation; Property; Pseudomonas aeruginosa; Pseudomonas syringae; Research; Role; Staphylococcus aureus; Structure; Surface; System; Testing; Theoretical Studies; Vertical Disease Transmission; Virulent; Virus; adaptive immunity; base; density; design; experimental study; models and simulation; pathogenic bacteria; resistance mechanism; theories; transmission process

ABSTRACT The viruses of bacteria and archaea, phage, are touted to be the most abundant organisms on Earth, and a great deal is known about their molecular biology, structure, and mechanisms of replication. Nevertheless there remain fundamental unanswered or incompletely answered questions about the population biology, ecological role, and evolution of these viruses. In this investigation we will address and provide answers to three of these fundamental questions: 1- What are the ecological, genetic and evolutionary conditions for lytic (virulent) phage to be maintained in and regulate the densities of bacterial populations? 2- Under what conditions will selection favor a temperate rather than a purely lytic mode of phage replication and transmission? 3- Under what conditions will selection by lytic and temperate phage favor the evolution and maintenance of CRISPR-Cas mediated adaptive immunity, rather than envelope or other constitutive resistance mechanisms? To address these questions, we will use mathematical and computer simulation models, the properties of which will be analyzed numerically with parameters estimated in the experimental systems that will be employed for population dynamic and evolutionary experiments. We will test the predictions (hypotheses) generated from our analysis of these models in populations of bacteria and phage maintained in liquid, surface, and semisolid culture. Based on the results of these experiments, we will modify our models to make them more realistic. The experiments will be done with Escherichia coli, Pseudomonas aeruginosa, Pseudomonas syringae, and Staphylococcus aureus and their lytic and/or temperate phage. In addition to their importance to academic ecology, population and evolutionary biology, the results of this basic science study may well have practical utility. This investigation will provide an empirically supported theory that could be used to facilitate the design and evaluation of programs to use phage for the treatment of bacterial infections in humans and domestic animals, and to control outbreaks of pathogenic bacteria in crops. !

抽象的 细菌和古细菌的病毒、噬菌体被认为是地球上最丰富的生物体， 人们对它们的分子生物学、结构和复制机制了解很多。尽管如此 关于种群生物学的基本问题仍然没有得到解答或不完全解答， 这些病毒的生态作用和进化。在本次调查中，我们将解决并提供答案 其中三个基本问题： 1- 生态、遗传和进化条件是什么？ 溶解性（剧毒）噬菌体要维持并调节细菌群体的密度？ 2- 下 什么条件将选择有利于噬菌体复制的温和而非纯粹裂解模式以及 传播？ 3- 在什么条件下裂解噬菌体和温带噬菌体的选择有利于进化 和维持 CRISPR-Cas 介导的适应性免疫，而不是包膜或其他组成型免疫 抵抗机制？为了解决这些问题，我们将使用数学和计算机模拟 模型，其属性将使用估计的参数进行数值分析 将用于种群动态和进化实验的实验系统。我们 将测试我们在人群中对这些模型进行分析所产生的预测（假设） 细菌和噬菌体维持在液体、表面和半固体培养物中。基于这些结果 实验中，我们将修改我们的模型，使其更加真实。实验将通过 大肠杆菌、铜绿假单胞菌、丁香假单胞菌、金黄色葡萄球菌及其 裂解和/或温带噬菌体。除了对学术生态、人口和 进化生物学，这项基础科学研究的结果很可能具有实际用途。这 调查将提供经验支持的理论，可用于促进设计和 使用噬菌体治疗人类和家庭细菌感染的方案的评估 动物，并控制农作物中致病菌的爆发。 ！