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 革兰氏阴性菌是一种独特的生存所必需的结构；它也是阻止细菌生长的物理屏障 许多种类的抗生素进入，从而使其无效。这项研究旨在 了解两个多蛋白质机器的结构和功能，这些机器负责两个蛋白质的生物发生 外膜的主要成分是脂多糖(LPS)和外膜蛋白(OMP)。至 了解每台机器中的蛋白质-蛋白质相互作用及其分子结构、生化和 将进行结构研究。为了剖析这些机器的各个部件的功能， 内毒素和有机磷农药转运和组装的中间体将从结构、生化和 在牢房里。更好地了解蛋白质的机制及其参与的过程可能会导致 最终可能被开发出来治疗革兰氏阴性感染的抑制剂的发现。

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 two 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, intermediates in transport and assembly of LPS and OMPs will be characterized structurally, biochemically, and in cells. 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.