Enteropathogenic Escherichia coli (EPEC) is a leading cause of severe human diarrhea, affecting mainly children, but also adults in the developing world. EPEC infects the enterocytes of the small intestine. Despite intensive research of this pathogen, the virulence mechanisms underlying the infection process are still largely obscure. The main objective of our research was to investigate the hypothesis that EPEC hijacks endocytic elements at infection sites to promote successful infection of its epithelial host. Using live cell confocal imaging we were able to show that EPEC induces the clustering of transferrin receptors, a very well characterized receptor that utilizes clathrin-mediated endocytosis, its specific adaptor protein TTP (SH3BP4), small GTPase proteins involved in internalization and recycling (Rab5 and Rab11, respectively). These processes were partly dependent on the translocation of a specific protein effector, EspF, into the host. Using FACS analysis we show that EPEC induces the uptake of Tfn into its host. These results imply that EspF is involved in triggering endocytosis, and endosomal remodeling at bacterial infection sites. Importantly, all these effects have been observed to occur early upon bacterial contacting the host’s plasma membrane, emphasizing their importance in establishing a successful infection and colonization of the host. A comprehensive understanding of the molecular and cellular mechanisms underlying these processes is highly important to obtain deeper insights into EPEC pathogenesis, and for developing novel antimicrobial therapeutics.
