Identifying limitations on microbial host jumps

确定微生物宿主跳跃的限制

• 批准号: 10715587
• 负责人: Talia Karasov
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715587
• 关键词: Address; Bacteria; Data; Environment; Evolution; Genetic; Genetic Variation; Genome; Goals; Horizontal Gene Transfer; Knowledge; Lead; Methods; Microbe; Organism; Population; Pseudomonas; Research; Specificity; System; Variant; Work; bacterial genetics; comparative genomics; cross-species transmission; functional genomics; genome-wide analysis; host-associated microbial communities; improved; microbial host; pathogen; pathogenic bacteria; prevent; programs

Of all the potential pathogens around us, we, like other multicellular species, can typically be infected by only a small subset. However, when a microbe manages to break such host barriers, it can quickly spread through the new host population. To predict when a pathogen will make a host jump, we need to understand what limits pathogen adaptation to different host environments. My research program focuses on investigating the factors that limit the adaptation of microbes to new host environments. Specifically, I address this question from the perspective of an evolutionary geneticist and microbiologist. I identify bacterial genetic mechanisms important for colonizing different hosts and use comparative and functional genomics to understand how they evolve. Recent work from myself and others demonstrated that both host genetics and the surrounding microbes influence the ability of a pathogen to move between hosts. The relative importance of host genetics and surrounding organisms as well as interactions between these factors are largely unknown. I recently developed a study system in the broad host range bacterial genus Pseudomonas that lays the groundwork for studying what limits the adaptation of pathogens to new hosts. My lab is now developing methods to identify genome-wide those loci in Pseudomonas important for colonizing different host environments. We have also curated natural variation data for thousands of Pseudomonas genomes collected from diverse hosts. Ongoing efforts are determining the associations between Pseudomonas genetic variation and differences in pathogen specificity. Over the next five years, the focus of my research program is to determine the relative importance of host genetics and surrounding microbes in limiting Pseudomonas adaptation to new hosts. To address this question, I will lead projects under three broad themes: (1) identify how surrounding microbes constrain evolution of Pseudomonas to a new host (2) determine how the genetic requirements for colonization change across host species (3) determine how horizontal gene transfer influences Pseudomonas adaptation to new hosts. Together these three projects will contribute to our understanding of how host genetics and the surrounding microbes influence Pseudomonas adaptation. I have selected these projects to start my lab because the question of what limits bacterial adaptation is a question generalizable to all bacteria. The mechanisms we discover are likely to be relevant to the study of other bacteria as many bacterial species share mechanisms of colonization, and this work is also relevant more broadly to general questions about niche evolution. My long-term objective is to use the knowledge gained from these studies to predict which microbes will undergo host jumps.

在我们周围的所有潜在病原体中，我们像其他多细胞物种一样，通常只能感染 小子集。但是，当微生物设法打破了这种宿主障碍时，它可以迅速通过 新的寄主人群。要预测病原体何时会跳跃，我们需要了解什么限制 病原体适应不同的宿主环境。 我的研究计划重点是研究限制微生物适应新宿主的因素 环境。具体而言，我从进化遗传学家和 微生物学家。我确定细菌遗传机制对于在不同的宿主定居并使用很重要 比较和功能基因组学了解它们的发展方式。我和他人的最新工作 证明宿主遗传学和周围微生物都会影响病原体移动的能力 主机之间。宿主遗传学和周围生物以及相互作用的相对重要性 这些因素之间在很大程度上未知。我最近在广泛的宿主范围内开发了一个研究系统 细菌属假单胞菌为研究什么限制了病原体适应的基础 新主机。我的实验室现在正在开发识别全基因组的方法 殖民不同的主机环境。我们还为数千个策划了自然变异数据 从不同宿主收集的假单胞菌基因组。持续的努力正在确定 假单胞菌遗传变异和病原体特异性的差异。 在接下来的五年中，我的研究计划的重点是确定主机的相对重要性 遗传学和周围的微生物限制了对新宿主的假单胞菌适应。为了解决这个问题， 我将在三个广泛的主题下领导项目：（1）确定周围微生物如何限制的演变 新宿主的假单胞菌（2）确定宿主的遗传需求如何变化 物种（3）确定水平基因转移如何影响假单胞菌适应新宿主。 这三个项目将共同有助于我们对寄主遗传学和周围环境的理解 微生物会影响假单胞菌的适应性。我选择了这些项目来启动我的实验室，因为问题 细菌适应性的限制是所有细菌可推广的问题。我们发现的机制是 可能与其他细菌的研究有关 这项工作也与有关利基进化的一般问题更广泛地相关。我的长期目标 是利用从这些研究中获得的知识来预测哪些微生物将经历宿主跳跃。