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.

在我们周围所有潜在的病原体中，我们和其他多细胞物种一样，通常只会感染一种 很小的子集。然而，当微生物设法打破这种宿主屏障时，它可以迅速通过 新的寄主种群。为了预测病原体何时会使宿主跳跃，我们需要了解什么限制 病原菌对不同寄主环境的适应性。 我的研究计划重点是调查限制微生物适应新宿主的因素 环境。具体地说，我从进化遗传学家的角度来回答这个问题 微生物学家。我确定了细菌遗传机制对不同宿主的定植和使用非常重要 比较基因组学和功能基因组学，以了解它们是如何进化的。我和其他人最近的工作 证明宿主遗传和周围的微生物都影响病原体的移动能力。 在主机之间。寄主遗传学和周围生物以及相互作用的相对重要性 这些因素之间的关系在很大程度上是未知的。我最近在广泛的宿主范围内开发了一个研究系统 假单胞菌属为研究限制病原体适应的因素奠定了基础 新主人。我的实验室现在正在开发方法来识别全基因组范围内的那些在假单胞菌中对 在不同的宿主环境中定居。我们还为数以千计的 采集自不同寄主的假单胞菌基因组。正在进行的努力正在确定两者之间的联系 假单胞菌的遗传变异和病原菌特异性的差异。 在接下来的五年里，我的研究计划的重点是确定东道主的相对重要性 限制假单胞菌适应新宿主的遗传学和周围微生物。为了解决这个问题， 我将在三大主题下领导项目：(1)确定周围的微生物如何限制进化 假单胞菌对新宿主的影响(2)决定了在不同宿主间对定殖的遗传要求如何变化 物种(3)决定水平基因转移如何影响假单胞菌对新宿主的适应。 这三个项目将有助于我们理解宿主遗传学和周围环境 微生物影响假单胞菌的适应。我之所以选择这些项目来开始我的实验室，是因为 是什么限制了细菌的适应，这是一个对所有细菌都适用的问题。我们发现的机制是 可能与其他细菌的研究有关，因为许多细菌物种具有共同的定植机制， 这项工作也更广泛地与关于生态位进化的一般问题相关。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。