Molecular mechanisms of evolution at the host-microbe interface

项目摘要 微生物和它们的动物宿主编码大量的蛋白质来感知、操纵和 互相防御。这些交互作用的结果可能意味着差异 在互惠互利的交换和致命的感染之间。上皮表面提供了 宿主和不同共生细菌群落之间的首次接触点，在 除了形成对抗细菌病原体的关键屏障外。虽然主机和 这些界面上的微生物蛋白质可以在这些界面之间和内部快速进化。 在种群中，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。我们将首先综合应用 确定上皮细胞多样性的系统发育和实验方法 表面蛋白介导的细胞间黏附和人相关病毒的毒力 细菌病原体。在第二条研究中，我们将确定灵长类的进化是如何 分泌的免疫蛋白调节细菌的破坏和防御功能。 这些项目还将利用实验室中的实验进化来追踪 细菌对抗菌酶的实时适应机制。这项研究 该计划将促进我们对进化的宿主-微生物系统的基本理解 并加快诊断和抗击日益增长的细菌威胁的战略 传染病。

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.