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Enterohemorrhagic  Escherichia coli  (EHEC) are major food-borne pathogens whose survival and virulence in the human digestive tract remain unclear owing to paucity of relevant models. EHEC interact with the follicle-associated epithelium of Peyer’s patches of the distal ileum and translocate across the intestinal epithelium  via  M-cells, but the underlying molecular mechanisms are still unknown. Here, we investigated the involvement of Long polar fimbriae (Lpf) in EHEC pathogenesis. Of the 236 strains tested, a significant association was observed between the presence of  lpf  operons and pathogenicity. In sophisticated  in vitro  models of the human gastro-intestinal tract,  lpf  expression was induced during transit through the simulated stomach and small intestine, but not in the colonic compartment. To investigate the involvement of Lpf in EHEC pathogenesis,  lpf  isogenic mutants and their relative trans-complemented strains were generated. Translocation across M-cells, interactions with murine ileal biopsies containing Peyer’s patches and the number of hemorrhagic lesions were significantly reduced with the  lpf  mutants compared to the wild-type strain. Complementation of  lpf  mutants fully restored the wild-type phenotypes. Our results indicate that (i) EHEC might colonize the terminal ileum at the early stages of infection, (ii) Lpf are an important player in the interactions with Peyer’s patches and M-cells, and could contribute to intestinal colonization.

Enterohemorrhagic Escherichia coli pathogenesis: role of Long polar fimbriae in Peyer’s patches interactions