Understanding events at the cell surface during autotransporter biogenesis

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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.