Propionate Induces Virulent Properties of Crohn’s Disease-Associated Escherichia coli

Abstract

Crohn’s disease (CD) is a severe chronic immune-mediated granulomatous inflammatory disease of the gastrointestinal tract. The mechanisms of CD pathogenesis remain obscure. Metagenomic analysis of samples from CD patients revealed that several of them have the elevated level of Escherichia coli with adhesive–invasive phenotype (AIEC). Previously, we isolated an E. coli strain CD isolate ZvL2 from a patient with CD, which features AIEC phenotype. Here, we demonstrate that prolonged growth on propionate containing medium stimulates virulent properties of CD isolate ZvL2, while prolonged growth on glucose reduces these properties to levels indistinguishable from laboratory strain K-12 MG1655. Propionate presence also boosts the ability of CD isolate ZvL2 to penetrate and colonize macrophages. The effect of propionate is reversible, re-passaging of CD isolate on M9 medium supplemented with glucose leads to the loss of its virulent properties. Proteome analysis of CD isolate ZvL2 growth in medium supplemented with propionate or glucose revealed that propionate induces expression porins OmpA and OmpW, transcription factors PhoP and OmpR , and universal stress protein UspE , which were previously found to be important for macrophage colonization by enteropathogenic bacteria.

Influenza Virus Infection Impairs the Gut’s Barrier Properties and Favors Secondary Enteric Bacterial Infection through Reduced Production of Short-Chain Fatty Acids

“…SCFAs can also prevent the abnormal expansion of antibiotic-resistant strains of Enterobacteriaceae, in part by increasing intracellular acidification (49). SCFAs (including propionate) have also been shown to regulate (favor) the growth and virulence of enteric pathogens, such as enterohemorrhagic and adherent-invasive E. coli (50,51). In our experimental model, mice fed SCFAs before an S. Typhimurium infection did not show a lower degree of local bacterial colonization, indicating a lack of a direct effect on bacterial growth.…”

Metabolic Phenotypes as Potential Biomarkers for Linking Gut Microbiome With Inflammatory Bowel Diseases

“…Although considered to be anti-inflammatory as butyrate (Tedelind et al, 2007 ), some of its effects on the immune cells are opposite to the ones of butyrate (Cavaglieri et al, 2003 ). Recently, propionate was shown to promote the virulent properties of CD-associated Escherichia coli (Ormsby et al, 2020 ; Pobeguts et al, 2020 ), the key taxon linked to the disease in previous studies.…”

The multifaceted virulence of adherent-invasive Escherichia coli

“… 28 Similarly, propionate was shown to promote the virulence and persistence of AIEC in the gut. 95 , 96 Interestingly, propionate did not increase the adhesion and invasion of epithelial cells by commensal E. coli , suggesting that this adaptation is unique to AIEC. 96 However, the modulation of AIEC virulence by SCFAs was shown to be largely dependent on the gut biogeography.…”

“… 95 , 96 Interestingly, propionate did not increase the adhesion and invasion of epithelial cells by commensal E. coli , suggesting that this adaptation is unique to AIEC. 96 However, the modulation of AIEC virulence by SCFAs was shown to be largely dependent on the gut biogeography. 97 For example, flagellar motility is increased under pH and SCFA concentrations mimicking that of the ileum, while the inverse is observed with colon mimicry.…”