Outer Membrane Biogenesis: New Antibiotic Targets

项目摘要/摘要 耐药革兰氏阴性菌感染严重威胁人类健康。外膜的外膜 革兰氏阴性细菌是一种独特的生存所必需的结构；它也是一种物理屏障 阻止许多类别的抗生素进入，从而使其无效。这项研究是针对 了解三种多蛋白质机器的结构和功能 外膜的两种主要成分--内毒素和外膜的生物发生 蛋白质(OMPS)。了解每台机器及其分子内的蛋白质-蛋白质相互作用 将进行结构、生化和结构研究。剖析个人的功能 这些机器的组件、内毒素和OMPS的组装将在体外重组。更好的 对蛋白质机制及其参与的过程的了解可能会导致 发现最终可能被开发用于治疗革兰氏阴性感染的抑制剂。

Project Summary/Abstract Antibiotic resistant Gram-negative infections pose a serious threat to human health. The outer membrane of Gram-negative bacteria is a unique structure essential for survival; it also functions as a physical barrier to block entry of many classes of antibiotics and thereby render them ineffective. This research is directed towards understanding the structure and function of three multi-protein machines responsible for the biogenesis of two major components of the outer membrane, lipopolysaccharide (LPS) and outer membrane proteins (OMPs). To understand the protein-protein interactions within each machine and their molecular structures, biochemical and structural studies will be undertaken. To dissect the functions of the individual components of these machines, the assembly of LPS and OMPs will be reconstituted in vitro. A better understanding of the protein machinery and the processes in which they are involved may lead to the discovery of inhibitors that could ultimately be developed to treat Gram-negative infections.