Anne Sophie Bourrel1, Laurent Poirel2,3, Guilhem Royer1,4,5, Mélanie Darty1, Xavier Vuillemin1, Nicolas Kieffer2,3, Olivier Clermont4, Erick Denamur4,6, Patrice Nordmann2,3, Jean-Winoc Decousser1,4. 1. Laboratoire de Bactériologie et d'Hygiène Hospitalière, CHU Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France. 2. Laboratoire Européen Associé INSERM, Emerging Antibiotic Resistance in Gram-Negative Bacteria, Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland. 3. National Reference Centre for Emerging Antibiotic Resistance (NARA), Fribourg, Switzerland. 4. IAME, UMR1137 INSERM, Université Paris Diderot, Université Paris Nord, Emerging Antibiotic Resistance in Gram-Negative Bacteria, Paris, France. 5. LABGeM, Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, Univ Evry, Université Paris-Saclay, Evry, France. 6. Laboratoire de Génétique Moléculaire, Hôpital Bichat, Assistance Publique - Hôpitaux de Paris, Paris, France.
Abstract
BACKGROUND: Beyond plasmid-encoded resistance (mcr genes) prevalence in strain collections, large epidemiological studies to estimate the human burden of colistin-resistant Escherichia coli gut carriage are lacking. OBJECTIVES: To evaluate the prevalence of colistin-resistant E. coli carriage in inpatients and decipher the molecular support of resistance and the genetic background of the strains. METHODS: During a 3 month period in 2017, we prospectively screened patients in six Parisian hospitals for rectal carriage of colistin-resistant E. coli using a selective medium, a biochemical confirmatory test and MIC determination. WGS of the resistant strains and their corresponding plasmids was performed. RESULTS: Among the 1217 screened patients, 153 colistin-resistant E. coli strains were isolated from 152 patients (12.5%). The mcr-1 gene was identified in only seven isolates (4.6%) on different plasmid scaffolds. The genetic background of these MCR-1 producers argued for an animal origin. Conversely, the remaining 146 colistin-resistant E. coli exhibited a phylogenetic distribution corresponding to human gut commensal/clinical population structure (B2 and D phylogroup predominance); 72.6% of those isolates harboured convergent mutations in the PmrA and PmrB proteins, constituting a two-component system shown to be associated with colistin resistance. CONCLUSIONS: We showed that the occurrence at a high rate of colistin resistance in human faecal E. coli is the result of two distinct evolutionary pathways, i.e. the occurrence of chromosomal mutations in an endogenous E. coli population and the rare acquisition of exogenous mcr-1-bearing strains probably of animal origin. The involved selective pressures need to be identified in order to develop preventative strategies.
BACKGROUND: Beyond plasmid-encoded resistance (mcr genes) prevalence in strain collections, large epidemiological studies to estimate the human burden of colistin-resistant Escherichia coli gut carriage are lacking. OBJECTIVES: To evaluate the prevalence of colistin-resistant E. coli carriage in inpatients and decipher the molecular support of resistance and the genetic background of the strains. METHODS: During a 3 month period in 2017, we prospectively screened patients in six Parisian hospitals for rectal carriage of colistin-resistant E. coli using a selective medium, a biochemical confirmatory test and MIC determination. WGS of the resistant strains and their corresponding plasmids was performed. RESULTS: Among the 1217 screened patients, 153 colistin-resistant E. coli strains were isolated from 152 patients (12.5%). The mcr-1 gene was identified in only seven isolates (4.6%) on different plasmid scaffolds. The genetic background of these MCR-1 producers argued for an animal origin. Conversely, the remaining 146 colistin-resistant E. coli exhibited a phylogenetic distribution corresponding to human gut commensal/clinical population structure (B2 and D phylogroup predominance); 72.6% of those isolates harboured convergent mutations in the PmrA and PmrB proteins, constituting a two-component system shown to be associated with colistin resistance. CONCLUSIONS: We showed that the occurrence at a high rate of colistin resistance in human faecal E. coli is the result of two distinct evolutionary pathways, i.e. the occurrence of chromosomal mutations in an endogenous E. coli population and the rare acquisition of exogenous mcr-1-bearing strains probably of animal origin. The involved selective pressures need to be identified in order to develop preventative strategies.
Authors: Alejandro Gallardo; María-Rocío Iglesias; María Ugarte-Ruiz; Marta Hernández; Pedro Miguela-Villoldo; Gloria Gutiérrez; David Rodríguez-Lázaro; Lucas Domínguez; Alberto Quesada Journal: Antimicrob Agents Chemother Date: 2021-03-08 Impact factor: 5.191
Authors: Giorgio Mattiuz; Sabrina Nicolò; Alberto Antonelli; Tommaso Giani; Ilaria Baccani; Antonio Cannatelli; Ann Maria Clemente; Giuseppe Castronovo; Michele Tanturli; Federico Cozzolino; Gian Maria Rossolini; Maria Gabriella Torcia Journal: Infect Immun Date: 2020-07-21 Impact factor: 3.441
Authors: Isidro García-Meniño; Dafne Díaz-Jiménez; Vanesa García; María de Toro; Saskia C Flament-Simon; Jorge Blanco; Azucena Mora Journal: Front Microbiol Date: 2019-11-01 Impact factor: 5.640