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mcr-9, an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin.

  • Kieffer N Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
  • Royer G Laboratoire de Bactériologie et d'Hygiène-Hospitalière, CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Decousser JW Laboratoire de Bactériologie et d'Hygiène-Hospitalière, CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Bourrel AS Laboratoire de Bactériologie et d'Hygiène-Hospitalière, CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France.
  • Palmieri M Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
  • Ortiz De La Rosa JM Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
  • Jacquier H IAME, UMR1137 INSERM, Université Paris Diderot, Université Paris Nord, Emerging Antibiotic Resistance in Gram-Negative Bacteria, Paris, France.
  • Denamur E IAME, UMR1137 INSERM, Université Paris Diderot, Université Paris Nord, Emerging Antibiotic Resistance in Gram-Negative Bacteria, Paris, France.
  • Nordmann P Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
  • Poirel L Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland laurent.poirel@unifr.ch.
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  • 2019-06-19
Published in:
  • Antimicrobial agents and chemotherapy. - 2019
Escherichia coli
MCR
MCR-9
colistin
plasmid
polymyxin
Anti-Bacterial Agents
Colistin
Drug Resistance, Bacterial
Escherichia coli
Escherichia coli Proteins
Ethanolaminephosphotransferase
Microbial Sensitivity Tests
Plasmids
Polymyxins
English The plasmid-located mcr-9 gene, encoding a putative phosphoethanolamine transferase, was identified in a colistin-resistant human fecal Escherichia coli strain belonging to a very rare phylogroup, the D-ST69-O15:H6 clone. This MCR-9 protein shares 33% to 65% identity with the other plasmid-encoded MCR-type enzymes identified (MCR-1 to -8) that have been found as sources of acquired resistance to polymyxins in Enterobacteriaceae Analysis of the lipopolysaccharide of the MCR-9-producing isolate revealed a function similar to that of MCR-1 by adding a phosphoethanolamine group to lipid A and subsequently modifying the structure of the lipopolysaccharide. However, a minor impact on susceptibility to polymyxins was noticed once the mcr-9 gene was cloned and produced in an E. coli K-12-derived strain. Nevertheless, we showed here that subinhibitory concentrations of colistin induced the expression of the mcr-9 gene, leading to increased MIC levels. This inducible expression was mediated by a two-component regulatory system encoded by the qseC and qseB genes located downstream of mcr-9 Genetic analysis showed that the mcr-9 gene was carried by an IncHI2 plasmid. In silico analysis revealed that the plasmid-encoded MCR-9 shared significant amino acid identity (ca. 80%) with the chromosomally encoded MCR-like proteins from Buttiauxella spp. In particular, Buttiauxella gaviniae was found to harbor a gene encoding MCR-BG, sharing 84% identity with MCR-9. That gene was neither expressed nor inducible in its original host, which was fully susceptible to polymyxins. This work showed that mcr genes may circulate silently and remain undetected unless induced by colistin.
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  • English
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https://sonar.ch/global/documents/2516
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