Outer Membrane Biogenesis: New Antibiotic Targets

项目概要/摘要 耐药革兰阴性菌感染对人类健康构成严重威胁。的外膜 革兰氏阴性菌是生存所必需的独特结构;它也可以作为一个物理屏障， 许多种类的抗生素进入，从而使它们无效。这项研究旨在 了解两个多蛋白质机器的结构和功能，负责两个 外膜的主要成分，脂多糖（LPS）和外膜蛋白（OMP）。到 了解每个机器内的蛋白质-蛋白质相互作用及其分子结构，生物化学和 将进行结构研究。为了剖析这些机器的各个部件的功能， LPS和OMP的转运和组装中的中间体将在结构上、生物化学上和生物化学上进行表征。 在细胞中。更好地理解蛋白质机制及其参与的过程可能会导致 到发现抑制剂，最终可以开发用于治疗革兰氏阴性菌感染。

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.