1. A single Proteus mirabilis lineage from human and animal sources: a hidden reservoir of OXA-23 or OXA-58 carbapenemases in Enterobacterales
- Author
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Pierre Bogaerts, Marisa Haenni, Elodie Couvé-Deacon, Rémy A. Bonnin, Jean-Yves Madec, Olivier Barraud, Lauraine Gauthier, Nicolas Fortineau, Philippe Glaser, Gaelle Cuzon, Laurent Dortet, Agnès B Jousset, Delphine Girlich, Thierry Naas, Youri Glupczynski, Team Resist [Le Kremlin-Bicêtre], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, French National Reference Center for Antibiotic Resistance: Carbapenemase producing Enterobacteriaceae [Le Kremlin-Bicêtre], Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS), Bacteriology-Hygiene unit [Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU UCL Namur, Unité Antibiorésistance et Virulence Bactériennes, Laboratoire de Lyon [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), This work was partially funded by the University Paris-Sud, France. LD, TN and RAB are members of the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT) supported by a grant from the French National Research Agency (ANR-10-LABX-33) and by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) DesInMBL [ANR-14-JAMR-002]., We want to thanks Pasteur International Bioressources Networking (PibNet, Paris, France) for providing whole genome sequencing facilities. We would like to thank the Transposon Registry for transposon nomenclature (https://transposon.lstmed.ac.uk/tn-registry). We thank INTEGRALL database for integron and gene cassette nomenclatures., ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), ANR-14-JAMR-0002,DesInMBL,Structure-guided design of pan inhibitors of metallo-ß-lactamases(2014), Université Paris-Sud - Paris 11 (UP11)-Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Unité Antibiorésistance et Virulence Bactériennes (AVB), Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), UCL - (MGD) Laboratoire de biologie clinique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Sud Orsay-Centre National de la Recherche Scientifique (CNRS), Bodescot, Myriam, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, and programmation conjointe européenne sur la résistance antimicrobienne - Structure-guided design of pan inhibitors of metallo-ß-lactamases - - DesInMBL2014 - ANR-14-JAMR-0002 - JPI AMR - VALID
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DNA, Bacterial ,0301 basic medicine ,clone (Java method) ,Lineage (genetic) ,Science ,030106 microbiology ,Antimicrobial resistance ,beta-Lactamases ,Article ,03 medical and health sciences ,Plasmid ,Bacterial Proteins ,Belgium ,Recombinase ,polycyclic compounds ,Animals ,Humans ,Clinical microbiology ,Proteus mirabilis ,Gene ,Genetics ,Multidisciplinary ,biology ,Phylogenetic tree ,integumentary system ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Chromosomes, Bacterial ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,030104 developmental biology ,Composite transposon ,Genes, Bacterial ,DNA Transposable Elements ,bacteria ,Medicine ,France ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Plasmids - Abstract
In Enterobacterales, the most common carbapenemases are Ambler’s class A (KPC-like), class B (NDM-, VIM- or IMP-like) or class D (OXA-48-like) enzymes. This study describes the characterization of twenty-four OXA-23 or OXA-58 producing-Proteus mirabilis isolates recovered from human and veterinary samples from France and Belgium. Twenty-two P. mirabilis isolates producing either OXA-23 (n = 21) or OXA-58 (n = 1), collected between 2013 and 2018, as well as 2 reference strains isolated in 1996 and 2015 were fully sequenced. Phylogenetic analysis revealed that 22 of the 24 isolates, including the isolate from 1996, belonged to a single lineage that has disseminated in humans and animals over a long period of time. The blaOXA-23 gene was located on the chromosome and was part of a composite transposon, Tn6703, bracketed by two copies of IS15∆II. Sequencing using Pacbio long read technology of OXA-23-producing P. mirabilis VAC allowed the assembly of a 55.5-kb structure encompassing the blaOXA-23 gene in that isolate. By contrast to the blaOXA-23 genes, the blaOXA-58 gene of P. mirabilis CNR20130297 was identified on a 6-kb plasmid. The acquisition of the blaOXA-58 gene on this plasmid involved XerC-XerD recombinases. Our results suggest that a major clone of OXA-23-producing P. mirabilis is circulating in France and Belgium since 1996.
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- 2020