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.

项目概要/摘要 在过去的几十年里，细菌不仅作为病原体而且作为有益生物体的重要性， 已被阐明。然而，很明显，细菌的多样性和进化更重要。 比最初想象的复杂。因为大多数系统不允许集成多种方法， 关于细菌进化仍有许多基本问题有待解答。具体来说， 细菌如何在自然环境中进化以及是什么驱动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 生活方式。它们具有自由生活、共生和致病的能力，这意味着这些生物体具有高度 适应性强，但影响其进化的因素仍然是个谜。了解机会性细菌 进化很重要，因为它们会导致危险的医院获得性感染 在世界范围内，通常是具有多重耐药性的超级细菌。 细菌进化的研究主要使用比较基因组方法或体外进行 实验进化。然而，机会细菌的多功能性和复杂性，以及它们的 与动物宿主的关系，需要更现实的实验环境。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、体外和体内 分析。我们研究的关键是我们研究相互作用的特定实验进化框架 四个关键参与者之间：i）机会性细菌，ii）其环境捕食者，iii）动物宿主 iv) 动物宿主微生物群。我们追求多方法策略的能力归功于我们易于处理的模型 系统。我们的细菌模型系统，粘质沙雷氏菌和铜绿假单胞菌，无处不在 人类以及许多其他生物体的环境和多重耐药性机会病原体。 我们将使用蜜蜂作为我们的宿主模型系统（Apis mellifera），这是本研究的最佳选择，因为 它们提供了研究机会细菌进化和宿主微生物的自然环境 易于处理、具有成本效益、高度可复制且易于操纵的交互。重要的是， 蜜蜂微生物群是一个稳定的群落，也很容易操纵。我们的新颖方法和 系统将使我们能够解决我们对细菌进化的理解中的许多基本差距，包括 推动机会性细菌进化的力量，这些细菌表现出生活方式的改变。特别是，我们将 确定哪些基因涉及多种生活方式，哪些适应力和相关的权衡 推动机会性细菌的进化，以及在暴露于波动的情况下会发挥哪些功能 环境和不断变化的选择压力。结果将产生重要的根本性影响，但也 健康影响，因为它们将揭示对宿主定植和毒力重要的特征，可用于 制定对抗多重耐药机会性细菌感染的新策略。