Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism

Guillaume Dalmasso (1) , Racha Beyrouthy (1, 2) , Sandrine Brugiroux (1) , Etienne Ruppé (3, 4, 5) , Laurent Guillouard (2) , Virginie Bonnin (1) , Pierre Saint-Sardos (1) , Amine Ghozlane (6) , Vincent Gaumet (7) , Nicolas Barnich (1) , Julien Delmas (1) , Richard Bonnet (1, 2)

1 M2iSH - Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
2 CNR - Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand]
3 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
4 DEBRC - Département d'Epidemiologie, Biostatistique et Recherche Clinique
5 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
6 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
7 IMoST - Imagerie Moléculaire et Stratégies Théranostiques

Background The plasmid-mediated resistance gene mcr-1 confers colistin resistance in Escherichia coli and paves the way for the evolution to pan-drug resistance. We investigated the impact of mcr-1 in gut colonization in the absence of antibiotics using isogenic E. coli strains transformed with a plasmid encoding or devoid of mcr-1. Results In gnotobiotic and conventional mice, mcr-1 significantly enhanced intestinal anchoring of E. coli but impaired their lethal effect. This improvement of intestinal fitness was associated with a downregulation of intestinal inflammatory markers and the preservation of intestinal microbiota composition. The mcr-1 gene mediated a cross-resistance to antimicrobial peptides secreted by the microbiota and intestinal epithelial cells (IECs), enhanced E. coli adhesion to IECs, and decreased the proinflammatory activity of both E. coli and its lipopolysaccharides. Conclusion Overall, mcr-1 changed multiple facets of bacterial behaviour and appeared as a factor enhancing commensal lifestyle and persistence in the gut even in the absence of antibiotics.

Keywords: mcr-1; Colistin; Antibiotic resistance; Antimicrobial peptides; Virulence; Inflammation; Microbiota; Escherichia coli; Commensalism

Domains: Life Sciences [q-bio]; Bioinformatics [q-bio.QM]

Guillaume Dalmasso, Racha Beyrouthy, Sandrine Brugiroux, Etienne Ruppé, Laurent Guillouard, et al.. Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism. Microbiome, 2023, 11 (1), pp.12. ⟨10.1186/s40168-022-01457-y⟩. ⟨pasteur-04086913⟩