title: The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo.
abstract: Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen and tightly adheres to human colonic epithelium by forming attaching/effacing lesions. To reach the epithelial surface, EHEC must penetrate the thick mucus layer protecting the colonic epithelium. In this study, we investigated how EHEC interacts with the intestinal mucus layer using mucin-producing LS174T colon carcinoma cells and human colonic mucosal biopsies. The level of EHEC binding and attaching/effacing lesion formation in LS174T cells was higher compared to mucin-deficient colon carcinoma cell lines, and initial adherence was independent of the presence of flagellin, Escherichia coli common pilus, or long polar fimbriae. Although EHEC infection did not affect gene expression of secreted mucins, it resulted in reduced MUC2 glycoprotein levels. This effect was dependent on the catalytic activity of the secreted metalloprotease StcE, which reduced the inner mucus layer and thereby promoted EHEC access and binding to the epithelium in vitro and ex vivo. Given the lack of efficient therapies against EHEC infection, StcE may represent a suitable target for future treatment and prevention strategies.
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.|School of Biological Sciences, University of East Anglia, Norwich, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Hews
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.|Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Seav-Ly
authors.initials: SL
authors.lastname: Tran
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Udo
authors.initials: U
authors.lastname: Wegmann
authors.affiliation: Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, UK.|Department of Gastroenterology, James Paget University Hospital, Great Yarmouth, UK.
authors.forename: Bernard
authors.initials: B
authors.lastname: Brett
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.|Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Alistair D S
authors.initials: ADS
authors.lastname: Walsham
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Devon
authors.initials: D
authors.lastname: Kavanaugh
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich, UK.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Ward
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Juge
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.|Gut Health and Food Safety Programme, Institute of Food Research, Norwich, UK.
authors.forename: Stephanie
authors.identifier: 0000-0003-3260-9112
authors.initials: S
authors.lastname: Schüller
mesh_terms: D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D018938:Caco-2 Cells; D002460:Cell Line; D003106:Colon / Q000382:microbiology / Q000473:pathology; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology*; D019453:Escherichia coli O157 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism; D005408:Flagellin / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D055262:Mucin-2 / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C524625:MUC2 protein, human; D055262:Mucin-2; D005408:Flagellin; D008666:Metalloendopeptidases; C465555:StcE protein, E coli
keywords: EHEC; IVOC; adherence; colonic epithelium; metalloprotease; mucus