Understanding events at the cell surface during autotransporter biogenesis

为了生存，细菌必须产生位于其细胞表面的蛋白质，这些蛋白质在一个称为分泌的过程中被释放到外部环境中。为了将蛋白质从细胞内部转移到表面，细菌必须将它们跨膜运输，这实际上构成了分泌的障碍。因此，细菌进化出了专门的机器，使它们能够在膜上移动蛋白质。一种这样的机制是自动传输系统。这是革兰氏阴性细菌中使用最广泛的蛋白质分泌系统。这项提案的总体目标是深入分析自体转运蛋白分泌的某些方面。对这些蛋白质的研究，实际上是对一般分泌系统的研究，都是为了几个重要的目标。首先，由于细菌病原体需要输出蛋白质来影响毒力，对分泌系统的研究提供了关于特定属和物种的致病策略的信息。其次，对分泌系统的研究为在追求抗感染策略的过程中削弱细菌提供了新的机会。了解分泌系统的第三个好处是，这些系统可能被用作新型疫苗递送系统的一部分来递送外来抗原。了解自身转运蛋白的重要性体现在这样一个事实上，即在某些情况下，它们是基本的毒力因子，在另一些情况下，它们构成当前人类疫苗的一部分。

To survive bacteria must produce proteins which are located on their cell-surface and which are released into the external environment in a process termed secretion. In order to get the proteins from the inside of the cell to the surface the bacteria must transport them across membranes, which in effect actually pose a barrier to secretion. Thus bacteria have evolved specialized machines which allow them to move proteins across the membranes. One such mechanism is the autotransporter system. This is the most widely used protein secretion system within the Gram-negative bacteria. The overall objective of this proposal is an in-depth analysis of certain aspects of autotransporter protein secretion. The study of these proteins and in fact the study of secretion systems in general, is aimed at several important objectives. First, since bacterial pathogens need to export proteins to effect virulence the study of secretion systems provides information about the pathogenic strategies of the particular genus and species. Second, the study of secretion systems provides new opportunities to attenuate bacteria in the pursuit of anti-infective strategies. A third benefit of understanding secretion systems is that these systems can potentially be exploited for the delivery of foreign antigens as part of novel vaccine delivery systems. The importance of understanding the autotransporters is illustrated by the fact that in some cases these are essential virulence factors and in other cases they form part of current human vaccines.