Pathogenesis of Enterohemorrhagic Escherichia coli O157:H7 is mediated by the cytochrome P450 family in Caenorhabditis elegans animal model

Abstract

Abstract Foodborne pathogens, including enterohemorrhagic Escherichia coli (EHEC) O157:H7, may enter from the farm environment and foods via several different vectors and influence human health. Here, we employed Caenorhabditis elegans as a host model system and compared specific host responses during EHEC O157:H7 infection using whole-transcriptome analysis. To elucidate the immune pathways stimulated by EHEC O157:H7, we employed quantitative real-time polymerase chain reaction (qRT-PCR), transgenic worms, and RNAi. Whole-transcriptome analysis revealed that genes encoding the cytochrome P450 (CYP450) family were induced more than 10-fold during EHEC O157:H7 infection in C. elegans host models. Importantly, C. elegans mutants lacking CYP450 genes were highly susceptible to EHEC O157:H7 infection compared with wild-type N2 worms. Consistent with susceptibility tests, qRT-PCR results indicated that CYP450 loss-of-function mutations significantly affected the transcriptional induction of antimicrobial peptide genes, such as clec-60. Together, our results provide critical insights into host strategies for avoiding EHEC O157:H7 pathogenesis in the gastrointestinal tract via the cytochrome P450 family and highlights potential molecular targets for preventing the virulence of EHEC O157:H7 in foods.