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

摘要细菌和古细菌的病毒，噬菌体，被吹捧为最多的 地球上有丰富的生物，人们对它们的分子生物学也有很多了解， 结构和复制机制。尽管如此，仍然存在基本的 关于种群生物学的未回答或未完全回答的问题， 这些病毒的生态作用和进化。在这次调查中，我们将解决和 为这些基本问题中的三个提供答案：1-什么是生态， 裂解(毒力)噬菌体在和 调节细菌种群的密度？2-在什么条件下进行选择 支持温和的而不是纯粹的裂解模式的噬菌体复制 传播？3-在什么条件下会通过裂解和温带噬菌体进行选择 有利于CRISPR-Cas介导的适应性免疫的进化和维持，而不是 而不是包络或其他本构阻力机制？要解决这些问题 问题，我们将使用数学和计算机模拟模型，属性 将用实验中估计的参数对其进行数值分析 将用于种群动态和进化实验的系统。 我们将测试通过对这些模型的分析生成的预测(假设) 在维持在液体、表面和半固体中的细菌和噬菌体种群中 文化。根据这些实验的结果，我们将修改我们的模型以使 他们更现实。这些实验将用大肠杆菌、假单胞菌进行 铜绿假单胞菌、丁香假单胞菌和金黄色葡萄球菌及其裂解和/或 温带噬菌体。除了它们对学术生态的重要性外，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用价值 实用程序。这项研究将提供一个可以使用的经验支持的理论 帮助设计和评估使用噬菌体治疗霍奇金淋巴瘤的方案 人类和家畜的细菌感染，以及控制猪 农作物中的致病细菌。

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.