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

Propionic acid (PA) is a bacteria-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 were increased to mimic the human intestine, led to recovery of AIEC with significantly increased virulence. Similar phenotypic changes were observed outwith the murine model when AIEC was grown in culture with PA as the sole carbon source; such PA exposure also resulted in AIEC that persisted at 20-fold higher levels in vivo. RNA-sequencing identified upregulation of genes involved in biofilm formation, stress response, metabolism, membrane integrity and alternative carbon source utilization. PA exposure also increased virulence in a number of E. coli isolates from Crohn's disease patients. Removal of PA was sufficient to reverse these phenotypic changes. Our data indicate that exposure to PA results in AIEC resistance and increased virulence in its presence.