Oxygen and contact with human intestinal epithelium independently stimulate virulence gene expression in enteroaggregative Escherichia coli

Samuel J Ellis, Muhammad Yasir, Douglas F Browning, Stephen J W Busby, Stephanie Schüller

Research output: Contribution to journalArticlepeer-review


Enteroaggregative Escherichia coli (EAEC) are important intestinal pathogens causing acute and persistent diarrhoeal illness worldwide. Although many putative EAEC virulence factors have been identified, their association with pathogenesis remains unclear. As environmental cues can modulate bacterial virulence, we investigated the effect of oxygen and human intestinal epithelium on EAEC virulence gene expression to determine the involvement of respective gene products in intestinal colonisation and pathogenesis. Using in vitro organ culture of human intestinal biopsies, we established the colonic epithelium as the major colonisation site of EAEC strains 042 and 17-2. We subsequently optimised a vertical diffusion chamber system with polarised T84 colon carcinoma cells for EAEC infection and showed that oxygen induced expression of the global regulator AggR, aggregative adherence fimbriae, E. coli common pilus, EAST-1 toxin, and dispersin in EAEC strain 042 but not in 17-2. Furthermore, the presence of T84 epithelia stimulated additional expression of the mucinase Pic and the toxins HlyE and Pet. This induction was dependent on physical host cell contact and did not require AggR. Overall, these findings suggest that EAEC virulence in the human gut is modulated by environmental signals including oxygen and the intestinal epithelium.

Original languageEnglish
Article numbere13012
JournalCellular microbiology
Issue number6
Early online date15 Feb 2019
Publication statusPublished - Jun 2019

Bibliographical note

© 2019 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funding: BBSRC DTP studentship; MRC New Investigator Research Grant. Grant Number: MR/J002062/1; Darwin Trust of Edinburgh PhD studentship; Industrial Biotechnology Catalyst (Innovate UK, BBSRC, EPSRC)


  • Adhesins, Escherichia coli/genetics
  • Bacterial Toxins/metabolism
  • Cell Line, Tumor
  • Colon/microbiology
  • Enterotoxins/metabolism
  • Escherichia coli/genetics
  • Escherichia coli Infections/microbiology
  • Escherichia coli Proteins/genetics
  • Fimbriae, Bacterial/genetics
  • Gene Expression Regulation, Bacterial
  • Hemolysin Proteins/metabolism
  • Host-Pathogen Interactions
  • Humans
  • Intestinal Mucosa/microbiology
  • Intestine, Small/microbiology
  • Oxygen/metabolism
  • Polysaccharide-Lyases/metabolism
  • Serine Endopeptidases/metabolism
  • Trans-Activators/genetics
  • Virulence Factors/genetics


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