1. Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism
- Author
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Guillaume Dalmasso, Racha Beyrouthy, Sandrine Brugiroux, Etienne Ruppé, Laurent Guillouard, Virginie Bonnin, Pierre Saint-Sardos, Amine Ghozlane, Vincent Gaumet, Nicolas Barnich, Julien Delmas, Richard Bonnet, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), This study was supported by the Ministère de la Recherche et de la Technologie, the Inserm (UMR 1071), the INRAe (USC-2018), the French government’s IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25), the National Program ‘Microbiote’ Inserm, the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) programme TransComp-ESC-R of the European Commission, and a grant (‘DYASPEO’) from the national priority research program for antimicrobial resistance (PPR-AMR)., ANR-20-PAMR-0003,DYASPEO,Dynamics, AMR, spread, persistence, evolution, colonization, human, animal, environment(2020), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), and European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012)
- Subjects
Microbiology (medical) ,Inflammation ,Virulence ,Colistin ,Antibiotic resistance ,Microbiota ,[SDV]Life Sciences [q-bio] ,Escherichia coli ,Antimicrobial peptides ,mcr-1 ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Microbiology ,Commensalism - Abstract
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.
- Published
- 2023