Deciphering the processes of adaptation and exaptation driving the evolution of opportunism in bacteria

破译驱动细菌机会主义进化的适应和外延适应过程

• 批准号: 10654208
• 负责人: Kasie Tyler Raymann
• 金额: $ 6.77万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-13 至 2023-08-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10654208
• 关键词: Address; Animals; Apis; Attenuated; Automobile Driving; Bacteria; Bacterial Genome; Bacterial Infections; Bacterial Model; Biological Assay; Biological Models; Communities; Comparative Genomic Analysis; Complex; Dangerousness; Development; Environment; Evolution; Exhibits; Exposure to; General Practitioners; Generations; Genes; Genome; Genomic approach; Gnotobiotic; Health; In Vitro; Libraries; Life Style; Multi-Drug Resistance; Mutation; Nosocomial Infections; Organism; Pathogenicity; Phenotype; Predatory Behavior; Process; Pseudomonas aeruginosa; Research; Resistance; Role; Serratia marcescens; Sterility; Superbug; Symbiosis; System; Technology; Testing; Virulence; Work; comparative genomics; cost effective; driving force; fitness; fitness test; host colonization; host microbiome; host microbiota; host-microbe interactions; human pathogen; in silico; in vivo; insight; microbiota; mutant; mutualism; novel strategies; novel therapeutic intervention; opportunistic pathogen; pathogen; pressure; programs; trait

Project Summary/Abstract In the last few decades, the importance of bacteria, not only as pathogens but also as beneficial organisms, has been elucidated. However, it has become clear that bacterial diversity and evolution is much more complex than initially thought. Because most systems do not allow for the integration of multiple approaches, there are still many fundamental questions that remain to be answered about bacterial evolution. Specifically, how bacteria evolve in the natural environment and what drives the evolution of different lifestyles in bacteria. From an evolutionary perspective, opportunistic bacteria are complex entities because of their wide-range of lifestyles. Their ability to be free-living, commensal, and pathogenic means that these organisms are highly adaptable, but the factors that influence their evolution remain a mystery. Understanding opportunistic bacterial evolution is important because they are responsible for causing dangerous hospital-acquired infections worldwide and are often multidrug resistant superbugs. Studies of bacterial evolution are primarily conducted using comparative genomic approaches or in vitro experimental evolution. However, the versatility and complexity of opportunistic bacteria, as well as their relationships with animal hosts, requires more realistic experimental settings. Here, we have developed a unique research program that will integrate multiple approaches, including in silico, in vitro, and in vivo analyses. Key to our research is our specific experimental evolution framework to study the interactions between four key players: i) an opportunistic bacterium, ii) their environmental predators, iii) an animal host and iv) the animal host microbiota. Our ability to pursue a multi-approach strategy is due to our tractable model systems. Our bacterial model systems, Serratia marcescens and Pseudomonas aeruginosa, are ubiquitous environmental and multi-drug resistant opportunistic pathogens of humans as well as many other organisms. We will use honeybees as our host model system (Apis mellifera), which are optimal for this research because they offer a natural environment in which to study opportunistic bacterial evolution and host-microbe interactions that is tractable, cost-effective, highly replicable, and can be easily manipulated. Importantly, the honeybee microbiota is a stable community that can also be easily manipulated. Our novel approach and systems will allow us to address many fundamental gaps in our understanding of bacterial evolution, including the forces that drive the evolution of opportunistic bacteria that exhibit changing lifestyles. In particular, we will identify what genes are involved in versatile lifestyles, what adaptive forces and associated tradeoffs are driving the evolution of opportunistic bacteria, and what functions are exapted during exposure to fluctuating environments and changing selective pressures. Results will have important fundamental implications but also health implications as they will reveal traits important for host colonization and virulence, which can be used for the development of new strategies for combating multidrug resistant opportunistic bacterial infections.

项目总结/摘要 在过去的几十年里，细菌的重要性，不仅作为病原体，而且作为有益生物， 已被阐明。然而，很明显，细菌的多样性和进化远不止 比最初想象的要复杂。由于大多数系统不允许多种方法的集成， 关于细菌的进化，还有许多基本问题有待解答。具体地说， 细菌如何在自然环境中进化，以及是什么推动了细菌不同生活方式的进化。 从进化的角度来看，机会细菌是复杂的实体，因为它们具有广泛的 生命形式有些它们能够自由生活、繁殖和致病，这意味着这些生物体高度 适应性强，但影响它们进化的因素仍然是个谜。了解机会性细菌 进化是重要的，因为它们是导致危险的医院获得性感染的原因。 并且通常是多重耐药的超级细菌。 细菌进化的研究主要使用比较基因组方法或体外方法进行 实验进化然而，机会性细菌的多功能性和复杂性，以及它们的 与动物宿主的关系，需要更现实的实验设置。在这里，我们开发了一个 独特的研究计划，将整合多种方法，包括计算机模拟，体外和体内 分析。我们研究的关键是我们特定的实验进化框架来研究相互作用 在四个关键角色之间：i）机会主义细菌，ii）它们的环境捕食者，iii）动物宿主 和iv）动物宿主微生物群。我们能够追求多方法战略是因为我们的易处理的模型 系统.我们的细菌模型系统，粘质沙雷氏菌和铜绿假单胞菌，是无处不在的 环境和人类以及许多其他生物体的多重耐药机会病原体。 我们将使用蜜蜂作为我们的宿主模式系统（意大利蜜蜂），这是本研究的最佳选择，因为 它们提供了一个研究机会细菌进化和宿主微生物的自然环境 这种相互作用是易处理的、具有成本效益的、高度可复制的，并且可以容易地操纵。重要的是 蜜蜂微生物群是一个稳定的群落，也很容易被操纵。我们的新方法和 系统将使我们能够解决我们对细菌进化的理解中的许多根本差距，包括 驱动机会主义细菌进化的力量，表现出不断变化的生活方式。特别是要 确定什么基因参与了多样化的生活方式，什么适应力和相关的权衡是什么 驱动机会细菌的进化，以及在暴露于波动的环境中， 环境和不断变化的选择压力。结果将产生重要的基本影响，但也 健康影响，因为它们将揭示对宿主定殖和毒力重要的特征，这些特征可用于 开发新的策略来对抗多重耐药的机会性细菌感染。