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: 10006574
• 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/10006574
• 关键词: Address; Animals; Bacteria; Bacterial Proteins; Binding; Cell-Cell Adhesion; Cells; Communicable Diseases; Communities; Diagnosis; Disease; Enzymes; Epithelial; Epithelium; 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 微生物及其动物宿主编码许多蛋白质以感知，操纵和 互相防御。这些相互作用的结果可能意味着差异 在共同的交换和致命感染之间。上皮表面提供 宿主和各种共生细菌社区之间的首次接触点， 除了形成针对细菌病原体的关键障碍。虽然主持人和 这些接口处的微生物蛋白可以在之间和内部迅速发展 人口，这种多样性对免疫防御的影响在很大程度上是未知的。这 提案将利用宿主 - 微型障碍互动作为模型来研究 自适应蛋白进化的原因和后果。我们将首先应用综合 系统发育和实验方法，以确定上皮多样化 表面蛋白介导细胞细胞粘附和与人相关的毒力 细菌病原体。在第二条研究中，我们将确定灵长类动物的演变 分泌的免疫蛋白调节细菌破坏和防御功能。 这些项目还将在实验室中采用实验进化来追踪 实时对抗菌酶的细菌适应机制。这项研究 计划将促进我们对不断发展的宿主微型机构系统的基本理解 并加速策略来诊断和打击细菌的日益严重的威胁 传染病。