Edinburgh Napier University

  Enterohaemorrhagic E. coli O157:H7 is a major food-borne and environmental pathogen responsible for both sporadic cases and outbreaks of food poisoning which can lead to serious sequelae, such as haemolytic uraemic syndrome. The structural subunit of E. coli O157:H7 flagella is flagellin, which is both the antigenic determinant of the H7 serotype, an important factor in colonisation, and an immunomodulatory protein determined to be a major pro-inflammatory component through the instigation of host cell signalling pathways. Flagellin has highly conserved N and C-terminal regions that are recognised by the host cell pattern recognition receptor, toll-like receptor 5 (TLR5). Activation of this receptor triggers cell signalling cascades, which are known to activate host cell kinases and transcription factors that respond with the production of inflammatory mediators such as the chemokine interleukin-8 (IL-8), although the exact components of this pathway are not yet fully characterised. We demonstrate that E. coli O157:H7-derived flagellin induces rapid phosphorylation of the EGFR, as an early event in intestinal epithelial cell signalling, and that this is required for the release of pro-inflammatory cytokine IL-8.