Lay summary
Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are important causes of diarrhoeal disease and hemolytic uremic syndrome in New Zealand and worldwide. These bacterial pathogens stimulate the formation of protrusive structures called ‘pedestals’ that promote colonization of the apical surface of the intestinal epithelium. We hypothesise that pedestal formation involves bacterial exploitation of the host process of ‘polarized exocytosis’, which expands specific sites in the plasma membrane of the human cell. We further propose that EPEC and EHEC stimulate exocytosis by targeting a multi-protein host complex called the ‘exocyst’. We will use genetic, biochemical, and microscopy-based approaches to determine if the formation of pedestals involves bacterial subversion of the exocyst, identify microbial factors that elicit exocytosis, and elucidate how exocytosis promotes bacterial infection. We will also use a mouse model system to confirm that EPEC and EHEC induce polarized exocytosis in vivo.