Poster Presentation BACPATH 2017

Intestinal colonization traits of pandemic multidrug resistant Escherichia coli ST131 (#111)

Anu Chacko 1 , Sohinee Sarkar 2 , Melanie L. Hutton 3 , Dimitrios Vagenas 1 , Rinaldo Ruter 4 , Stephanie Schuller 4 5 , Dena Lyras 3 , Mark A. Schembri 6 , Makrina Totsika 1
  1. Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Qld, Australia
  2. Infection and Immunity program, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  3. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia
  4. Gut Health and Food Safety Programme, Institute of Food Research, Norwich, United Kingdom
  5. Norwich Medical School, University of East Anglia, Norwich,, United Kingdom
  6. School of Chemistry & Molecular Biosciences, and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Qld, Australia

Epidemiological studies point to the gut as a key reservoir of multidrug resistant Escherichia coli sequence type 131 (ST131), a globally dominant pathogenic clone causing urinary tract and bloodstream infections worldwide. However, not much is known about the factors driving intestinal carriage of E.coli ST131, particularly in a complex environment where there exists competition with other pathogens and commensal bacteria. Here we report a detailed investigation of the intestinal lifestyle of E.coli ST131.

Clinical ST131 isolates and type 1 fimbriae null mutants were assessed for colonisation of intestinal epithelia in vitro and in mouse intestinal colonisation models. Mouse gut tissue was examined by histology to determine pathology and localise ST131.These key findings were corroborated in mucus producing human cell lines and intestinal biopsies. Interestingly, we found that the ST131 strains adhered to and invaded into human intestinal epithelial cells more than probiotic and commensal strains. The reference ST131 strain EC958 established persistent intestinal colonisation in mice and expression of type 1 fimbriae mediated higher colonisation levels. Bacterial loads were highest in the distal parts of the mouse intestine and did not cause any obvious pathology. Further analysis revealed that EC958 could bind to both mucus and underlying human intestinal epithelia. Overall our findings demonstrate that the ST131 strains colonise the gut efficiently and are tropic to the distal parts of the mammalian intestine. ST131 is well tolerated in the intestine, thus permitting long-term persistence and dissemination within the community. The role of type 1 fimbriae as an intestinal colonisation factor suggests that novel inhibitors of the type 1 fimbrial adhesin FimH, currently developed as therapeutics for ST131 bladder infections and Crohn’s disease, could be used to limit ST131 intestinal burden.