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.

项目摘要/摘要 在过去的几十年中，细菌的重要性不仅是病原体，而且是有益的生物， 已经阐明了。但是，很明显，细菌多样性和进化要多得多 比最初想象的复杂。因为大多数系统不允许整合多种方法，所以 关于细菌进化，仍然有许多基本问题要回答。具体来说， 细菌如何在自然环境中进化，以及什么推动细菌中不同生活方式的演变。 从进化的角度来看，机会细菌是复杂的实体，因为它们的广泛范围 生活方式。它们具有自由生活，共同和致病性的能力意味着这些生物是高度的 适应能力，但是影响其进化的因素仍然是一个谜。了解机会细菌 进化很重要，因为它们负责引起危险的医院获得感染 在全球范围内，通常是抗多药的超级细菌。 细菌进化的研究主要是使用比较基因组方法或体外进行的 实验进化。但是，机会细菌的多功能性和复杂性及其 与动物宿主的关系需要更现实的实验环境。在这里，我们已经开发了 独特的研究计划，该计划将整合多种方法，包括硅，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 在四个主要参与者之间：i）机会细菌，ii）它们的环境掠食者，iii）动物宿主 和iv）动物宿主菌群。我们追求多重诉讼策略的能力是由于我们的可进行模型 系统。我们的细菌模型系统，Serratia Marcescens和铜绿假单胞菌无处不在 人类以及许多其他生物的环境和多药的机会病原体。 我们将使用Honeybees作为我们的宿主模型系统（API Mellifera），这对于这项研究是最佳的，因为 他们提供了一个自然环境，可以在其中研究机会性细菌进化和宿主 - 微叶 相互作用的相互作用，具有成本效益，高度可复制，可以轻松操纵。重要的是， Honeybee Microbiota是一个稳定的社区，也很容易被操纵。我们的新方法和 系统将使我们能够解决对细菌进化的理解，包括 驱动机会细菌演变的力量表现出改变的生活方式。特别是，我们会 确定哪些基因参与多功能生活方式，哪些适应力和相关的权衡是 推动机会细菌的演变，以及在暴露于波动期间的功能 环境和改变选择性压力。结果将具有重要的基本影响，但也将具有 健康的影响，因为它们将揭示对宿主殖民和毒力重要的特征，可用于 开发了对抗多药耐药的机会细菌感染的新策略。