Understanding the role of the outer membrane translocator in autotransporter biogenesis

为了生存，细菌必须产生位于其细胞表面并分泌到外部环境中的蛋白质。为了使蛋白质从细胞质到达细胞表面，细菌必须将它们运输穿过脂膜，脂膜实际上构成了分泌的屏障。因此，细菌已经进化出专门的机器，使它们能够将蛋白质穿过脂质膜。其中一个机制是自动转运系统。这是革兰氏阴性菌中最广泛使用的蛋白质分泌系统。本提案的总体目标是深入分析自转运蛋白分泌的某些方面。对这些蛋白质的研究以及实际上对一般分泌系统的研究旨在实现几个重要目标。首先，由于细菌病原体需要输出蛋白质来影响毒力，因此分泌系统的研究提供了有关特定属和种的致病策略的信息。其次，分泌系统的研究提供了新的机会，以减毒细菌在追求抗感染策略。了解分泌系统的第三个好处是，这些系统可以潜在地用于递送外源抗原，作为新型疫苗递送系统的一部分。了解自身转运蛋白的重要性可以通过以下事实来说明：在某些情况下，这些是必需的毒力因子，而在其他情况下，它们构成了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 secreted into the external environment. In order to get the proteins from the cytoplasm of the cell to the surface the bacterium must transport them across lipid membranes, which in effect actually pose a barrier to secretion. Thus bacteria have evolved specialized machineries which allow them to move proteins across the lipid 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