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

项目摘要/摘要 在过去的几十年里，细菌的重要性，不仅作为病原体，而且作为有益的生物体， 已被阐明。然而，很明显，细菌的多样性和进化要多得多 比最初想象的要复杂。因为大多数系统不允许集成多个方法， 关于细菌进化，仍有许多基本问题有待解答。具体来说， 细菌是如何在自然环境中进化的，以及是什么驱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 生活方式。它们自由生活、共生和致病的能力意味着这些有机体高度 适应能力强，但影响它们进化的因素仍然是个谜。了解机会主义细菌 进化很重要，因为它们是导致危险的医院获得性感染的罪魁祸首 而且经常是具有多重抗药性的超级细菌。 细菌进化的研究主要是利用比较基因组学方法或在体外进行的。 实验进化论。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，我们开发了一种 独特的研究计划，将整合多种方法，包括硅胶、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 以及iv)动物宿主微生物区系。我们之所以能够采取多途径战略，得益于我们易于驾驭的模式 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的环境和多重抗药性机会性病原体。 我们将使用蜜蜂作为我们的宿主模型系统(意大利蜜蜂)，这对本研究是最佳的，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。 易于处理、经济高效、高度可复制且易于操作的交互。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理解中的许多根本差距，包括 推动机会主义细菌进化的力量，这些细菌表现出不断变化的生活方式。特别是，我们将 确定哪些基因与多样化的生活方式有关，什么是适应性力量和相关的权衡 推动机会性细菌的进化，以及在暴露于波动中时哪些功能被排除 环境和不断变化的选择压力。结果将具有重要的根本性影响，但也 对健康的影响，因为它们将揭示对寄主殖民和毒力重要的特征，这些特征可用于 抗击多重耐药机会性细菌感染的新策略的开发。

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.