Protein secretion in bacterial pathogens

项目摘要 该项目汇集了UCSF的结构，生物化学，蛋白质组学和遗传学专业知识， 提供了一个详细的了解结构和翻译后调控的一个关键毒力因子， 结核分枝杆菌。有毒的细胞内细菌的一个标志是它们使用专门的分泌物 将蛋白质注入哺乳动物细胞的系统。在革兰氏阴性菌中已知多种这样的系统 （称为I-VI型和VIII-IX型）系统），但只有一种是专门在革兰氏阳性细菌中发现的： VII型分泌（T7 S）系统。结核分枝杆菌使用多个T7 S系统促进感染 通过效应物的分泌。事实上，主要的遗传差异之间的无害疫苗株卡介苗 和致病性M.结核病是ESX-1 T7 S系统的损失。T7 S对脓肿也是必需的 金黄色葡萄球菌和其他病原体的形成可能需要T7 S的毒力，因为这些系统 在革兰氏阳性细菌中广泛保守。在本提案中，我们的目标是建立在我们的初步数据， T7 S的基本机制，并解开这种复杂生物学的生化和结构基础， 机

Project Summary This project brings together structural, biochemical, proteomic and genetic expertise at UCSF to provide a detailed understanding of the structure and post-translational regulation of a key virulence factor in Mycobacterium tuberculosis. A hallmark of virulent, intracellular bacteria is their use of specialized secretion systems to inject proteins into mammalian cells. Multiple such systems are known in Gram-negative bacteria (termed the Type I-VI and VIII-IX) systems), but only one is found exclusively in Gram-positive bacteria: the type VII secretion (T7S) system. Mycobacterium tuberculosis uses multiple T7S systems to promote infection through secretion of effectors. In fact, the main genetic difference between the harmless vaccine strain BCG and pathogenic M. tuberculosis is the loss of the ESX-1 T7S system. T7S is also essential for abscess formation in Staphylococcus aureus and other pathogens may require T7S for virulence, as these systems are broadly conserved in Gram-positive bacteria. In this proposal we aim to build on our preliminary data regarding the basic mechanisms of T7S and unravel the biochemical and structural foundations of this complex biological machine.