How autotransporter proteins modulate bacteria–host interactions
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC.
- Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane QLD 4072, Australia.
Bacterial pathogens deploy an arsenal of virulence factors to establish infection and cause disease. At the front line of the infection process are bacterial surface components, which are responsible for host colonisation and pathogen adhesion. Autotransporter (AT) proteins are the largest group of surface adhesins in Gram-negative bacteria. These proteins play a central role in controlling bacterial interactions with their environment; they allow bacteria to aggregate with other bacteria, adhere to human cells, and form biofilms all key facilitators of bacterial persistence and pathogenesis. We previously elucidated the mechanism by which the AT adhesin Antigen43 (Ag43) from uropathogenic E. coli (UPEC) promotes bacterial aggregation/biofilm formation, by means of self-association between neighbouring cells. We have produced the structures of a further AT proteins and we are now starting to elucidate the mechanisms of action for diverse ATs. So far, we have found that different AT adhesins promote bacterial aggregation using subtle variations in this self-association mechanism compared to Ag43. We are also beginning to uncover in atomic detail how AT adhesins like UpaB and TibA bind epithelial surfaces. TibA is a multifunctional AT from enterotoxigenic E. coli(ETEC), the leading bacterial cause of diarrhea. This surface protein was known to be glycosylated by the cognate glycosyltransferase TibC. Our work is beginning to uncover how glycosylation regulates the function of multifunctional AT adhesins. This may represent a general mechanism for bacteria to regulate the virulence functions of the vast number of ATs expressed on their cell surface. Finally, we are using this new knowledge to successfully develop methods for disrupting AT function.