Propionic acid promotes the virulent phenotype of Crohn's disease-associated adherent-invasive Escherichia coli

Ormsby, M. et al. (2020) Propionic acid promotes the virulent phenotype of Crohn's disease-associated adherent-invasive Escherichia coli. Cell Reports, 30(7), 2297-2305.e5. (doi: 10.1016/j.celrep.2020.01.078) (PMID:32075765) (PMCID:PMC7034058)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McIntosh, Ms Anne and Ormsby, Dr Michael and Wall, Dr Daniel and Connolly, Dr James and HULME, Heather and Morrison, Dr Douglas and Gerasimidis, Professor Konstantinos and Walker, Professor Daniel and Roe, Professor Andrew and Hansen, Dr Richard and Carpena Garcia, Miss Nuria and Meikle, Dr Lynsey and Goldstone, Mr Robert and Johnson, Miss Sile and Wessel, Miss Hannah
Authors: Ormsby, M., Johnson, S. A., Carpena, N., Meikle, L. M., Goldstone, R. J., McIntosh, A., Wessel, H. M., Hulme, H. E., McConnachie, C. C., Connolly, J. P.R., Roe, A. J., Hasson, C., Boyd, J., Fitzgerald, E., Gerasimidis, K., Morrison, D., Hold, G. L., Hansen, R., Walker, D., Smith, D. G.E., and Wall, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Science and Engineering > Scottish Universities Environmental Research Centre
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cell Reports 30(7): 2297-2305.e5
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
167488Survival and dissemination of enteric pathogens through exploitation and inhibition of programmed cell death pathways in circulating immune cells.Daniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/K008005/1III - Bacteriology
173261Propionic acid use in agriculture and food production is driving evolution of novel Escherichia coli pathotypesDaniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/P003281/1III - Bacteriology
171637Molecular Functions in Disease PhD Studentship (2013-2017)Daniel WallWellcome Trust (WELLCOTR)102460/Z/13/ZRIII - Immunology