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，我们和其他多细胞物种一样，通常只能被一种 小子集然而，当一种微生物设法打破这种宿主屏障时，它可以迅速通过微生物传播。 新的宿主种群为了预测病原体何时会使宿主发生跳跃，我们需要了解 病原体适应不同的宿主环境。 我的研究项目集中于调查限制微生物适应新宿主的因素 环境.具体来说，我从进化遗传学家的角度来解决这个问题， 微生物学家我确定了细菌的遗传机制，重要的殖民不同的主机和使用 比较和功能基因组学来了解它们是如何进化的。我和其他人最近的工作 表明宿主遗传学和周围的微生物都会影响病原体的移动能力， 宿主之间。宿主遗传学和周围生物的相对重要性以及相互作用 这些因素之间的关系在很大程度上是未知的。我最近开发了一个学习系统， 细菌属假单胞菌，为研究限制病原体适应的因素奠定了基础， 新的宿主我的实验室现在正在开发方法，以确定全基因组的假单胞菌的重要基因座， 殖民于不同的宿主环境我们还策划了数千个自然变异数据， 从不同宿主收集的假单胞菌基因组。正在进行的努力正在确定 假单胞菌遗传变异与病原特异性差异。 在接下来的五年里，我的研究计划的重点是确定宿主的相对重要性， 遗传学和周围的微生物限制假单胞菌适应新的宿主。为了解决这个问题， 我将在三个广泛的主题下领导项目：（1）确定周围的微生物如何限制进化， 假单胞菌向新宿主的迁移（2）决定了定植的遗传要求如何在宿主间发生变化 物种（3）决定了水平基因转移如何影响假单胞菌适应新的宿主。 这三个项目将有助于我们了解宿主遗传学和周围环境是如何影响人类健康的。 微生物影响假单胞菌适应。我之所以选择这些项目来启动我的实验室， 是什么限制了细菌的适应性，这是一个可推广到所有细菌的问题。我们发现的机制是 可能与其他细菌的研究相关，因为许多细菌物种共享定殖机制， 这项工作也更广泛地涉及生态位进化的一般问题。我的长期目标 是利用这些研究中获得的知识来预测哪些微生物会经历宿主跳跃。