Molecular mechanisms of evolution at the host-microbe interface

宿主-微生物界面进化的分子机制

• 批准号: 10220998
• 负责人: Matthew Frederick Barber
• 金额: $ 36.57万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-02 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220998
• 关键词: Address; Animals; Bacteria; Bacterial Proteins; Binding; Cell-Cell Adhesion; Cells; Communicable Diseases; Communities; Diagnosis; Disease; Enzymes; Epithelial; Evolution; Genetic Variation; Health; Human; Immune; Immunity; Infection; Laboratories; Mediating; Membrane Proteins; Microbe; Modeling; Molecular; Outcome; Phylogenetic Analysis; Population; Predisposition; Primates; Proteins; Research; Resistance; Surface; System; Time; Virulence; antimicrobial; combat; commensal bacteria; microbial; pathogenic bacteria; pathogenic microbe; programs

Project Summary Microbes and their animal hosts encode numerous proteins to sense, manipulate, and defend against each other. The outcome of these interactions can mean the difference between a mutualistic exchange and a fatal infection. Epithelial surfaces provide the point of first contact between hosts and diverse communities of commensal bacteria, in addition to forming a critical barrier against bacterial pathogens. Although host and microbial proteins at these interfaces can evolve rapidly between and within populations, the impact of such diversity on immune defense is largely unknown. This proposal will leverage host-microbe barrier interactions as models to investigate the causes and consequences of adaptive protein evolution. We will first apply integrative phylogenetic and experimental approaches to determine how diversification of epithelial surface proteins mediates cell-cell adhesion and virulence of human-associated bacterial pathogens. In a second line of study, we will identify how evolution of primate secreted immunity proteins modulates bacterial destruction and defense functions. These projects will also employ experimental evolution in the laboratory to trace mechanisms of bacterial adaptation to antimicrobial enzymes in real time. This research program will advance our fundamental understanding of evolving host-microbe systems and accelerate strategies to diagnose and combat the growing threat of bacterial infectious disease.

项目摘要 微生物和它们的动物宿主编码许多蛋白质来感知、操纵和控制微生物。 互相防御。这些互动的结果可能意味着 互惠交换和致命感染之间的联系上皮表面提供了 宿主和不同的肠道细菌群落之间的第一次接触点， 除了形成抵抗细菌病原体的关键屏障之外。虽然东道主和 这些界面上的微生物蛋白质可以在它们之间和内部迅速进化， 然而，尽管这些生物多样性对免疫防御的影响在很大程度上是未知的。这 该提案将利用宿主-微生物屏障相互作用作为模型来研究 适应性蛋白质进化的原因和后果。我们将首先应用集成 系统发育和实验方法来确定上皮细胞的多样化 表面蛋白介导的细胞间粘附和人相关病毒毒力 细菌病原体在第二条研究路线中，我们将确定灵长类动物的进化 分泌的免疫蛋白调节细菌的破坏和防御功能。 这些项目还将在实验室中采用实验进化来追踪 细菌适应抗菌酶的机制在真实的时间。本研究 该计划将促进我们对不断演变的宿主微生物系统的基本理解 并加快诊断和打击日益增长的细菌威胁的战略， 传染病