Outer Membrane Biogenesis: New Antibiotic Targets

描述(申请人提供)：抗药性革兰氏阴性感染对人类健康构成严重威胁。革兰氏阴性细菌的外膜是生存所必需的独特结构；它还起到物理屏障的作用，阻止许多类别的抗生素进入，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，这些机器负责外膜的两个主要成分--脂多糖(LPS)和外膜蛋白(OMP)的生物发生。为了了解每台机器内的蛋白质-蛋白质相互作用及其分子结构，将进行生化和结构研究。为了剖析这些机器的各个部件的功能，将在体外重组脂多糖和OMPS的组装。更好地了解蛋白质机制及其参与的过程可能会导致发现最终可能被开发出来治疗革兰氏阴性菌感染的抑制剂。

DESCRIPTION (provided by applicant): 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, 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.