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Our research into pathogenic E. coli
Research in our laboratory aims at understanding molecular bacteria-host interactions under conditions similar to those in the human gut. This includes the presence of low oxygen levels, mucus and the microbiota. To achieve this, we use differentiated human colon cancer cell lines, stem cell-derived intestinal organoids, organ culture of intestinal biopsies and a microaerobic microbe-host co-culture system (VDC) as experimental models.
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Group Leader: Stephanie Schüller
View my research profileI am a cellular microbiologist and completed my PhD at the Julius-Maximilians-Universität Würzburg in Germany in 1997. I then moved to the UK and took up several postdoctoral positions at Imperial College and UCL in London before joining the Norwich Medical School in 2010.
Postgraduate Opportunities
Please get in touch if you would like to discuss potential PhD opportunities.
Enterohaemorrhagic E. coli (EHEC)
Our initial research has focussed on EHEC which is a major zoonotic pathogen and the main cause of acute kidney failure in children in the Western world. Our work has shown that EHEC gains access to the intestinal epithelium by degrading the mucus layer via the metalloprotease StcE. Tight bacterial binding to the epithelium is enhanced by the low oxygen levels in the gut which promote type III secretion of the EHEC receptor protein Tir. In addition, microaerobiosis promotes Shiga toxin translocation across the epithelium which increases the risk of developing kidney disease. Notably, Shiga toxin transport into the bloodstream is significantly linked to EHEC strains with high virulence. By using human colonoids we demonstrated that Shiga toxin transport is mediated by outer membrane vesicles.
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E. coli interactions with the microbiota
We have further studied the role of commensal gut bacteria in infection with diarrhoeagenic E. coli. To this aim, we have developed and optimised a microaerobic in vitro model which enables incubation of human intestinal epithelia with oxygen-sensitive gut commensals. Our studies have shown the importance of the mucus layer in E. coli colonisation resistance mediated by commensal Limosilactobacillus reuteri and Ruminococcus gnavus.
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Host-microbe interactions in Crohn’s disease and colon cancer
Current lab projects are investigating the impact of adherent-invasive E. coli (AIEC) and the microbiota in loss of epithelial barrier function and chronic inflammation in Crohn’s disease. To this aim, we have established human colonoids from Crohn’s patients and healthy donors as experimental models. In addition, we are determining how the colonic environment and microbiota affects the development of colorectal cancer by genotoxic E. coli.
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Select Publications
Krsek et al. (2023) Translocation of outer membrane vesicles from enterohemorrhagic Escherichia coli O157 across the intestinal epithelial barrier, Front Microbiol
McGrath et al. (2022) Development of a novel human intestinal model to elucidate the effect of anaerobic commensals on Escherichia coli infection, DMM
Ellis et al. (2020) Identification and characterisation of enteroaggregative Escherichia coli subtypes associated with human disease, Sci Rep
Hews et al. (2017) The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo, Cell Microbiol
Lewis et al. (2015) Enterohemorrhagic Escherichia coli colonization of human colonic epithelium in vitro and ex vivo, Infect Immun