Propionic Acid Promotes the Virulent Phenotype of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli
Michael J. Ormsby,
Síle A. Johnson,
Nuria Carpena,
Lynsey M. Meikle,
Robert J. Goldstone,
Anne McIntosh,
Hannah M. Wessel,
Heather E. Hulme,
Ceilidh C. McConnachie,
James P.R. Connolly,
Andrew J. Roe,
Conor Hasson,
Joseph Boyd,
Eamonn Fitzgerald,
Konstantinos Gerasimidis,
Douglas Morrison,
Georgina L. Hold,
Richard Hansen,
Daniel Walker,
David G.E. Smith,
Daniel M. Wall
Affiliations
Michael J. Ormsby
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Síle A. Johnson
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Nuria Carpena
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Lynsey M. Meikle
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Robert J. Goldstone
Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK
Anne McIntosh
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Hannah M. Wessel
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Heather E. Hulme
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Ceilidh C. McConnachie
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
James P.R. Connolly
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK; Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK
Andrew J. Roe
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Conor Hasson
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Joseph Boyd
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Eamonn Fitzgerald
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
Konstantinos Gerasimidis
Human Nutrition, School of Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
Douglas Morrison
Scottish Universities Environmental Research Centre, University of Glasgow, Glasgow G75 0QF, UK
Georgina L. Hold
Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
Richard Hansen
Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, 1345 Govan Road, Glasgow G51 4TF, UK
Daniel Walker
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK
David G.E. Smith
Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK
Daniel M. Wall
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow G12 8TA, UK; Corresponding author
Summary: Propionic acid (PA) is a bacterium-derived intestinal antimicrobial and immune modulator used widely in food production and agriculture. Passage of Crohn’s disease-associated adherent-invasive Escherichia coli (AIEC) through a murine model, in which intestinal PA levels are increased to mimic the human intestine, leads to the recovery of AIEC with significantly increased virulence. Similar phenotypic changes are observed outside the murine model when AIEC is grown in culture with PA as the sole carbon source; such PA exposure also results in AIEC that persists at 20-fold higher levels in vivo. RNA sequencing identifies an upregulation of genes involved in biofilm formation, stress response, metabolism, membrane integrity, and alternative carbon source utilization. PA exposure also increases virulence in a number of E. coli isolates from Crohn’s disease patients. Removal of PA is sufficient to reverse these phenotypic changes. Our data indicate that exposure to PA results in AIEC resistance and increased virulence in its presence. : The short chain fatty acid propionic acid is a bacterium-derived human intestinal antimicrobial and immune modulator used widely in Western food production and agriculture. Here, Ormsby et al. demonstrate that exposure to propionic acid induces virulence-associated phenotypic changes in Crohn’s disease-associated adherent-invasive Escherichia coli (AIEC). Keywords: adherent-invasive E. coli, Crohn's disease, short chain fatty acid, propionic acid
