1. Specificities and commonalities of carbapenemase producing Escherichia coli isolated in France from 2012 to 2015
- Author
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Nicolas Cabanel, Isabelle Rosinski-Chupin, Delphine Girlich, Rémy A. Bonnin, Saoussen Oueslati, Laurent Dortet, Pengdbamba Dieudonné Zongo, Mélanie Héry, Rafael Patiño-Navarrete, Thierry Naas, Philippe Glaser, 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-Saclay-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), 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, French National Reference Center for Antibiotic Resistance: Carbapenemase producing Enterobacteriaceae [Le Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), This work was supported by grants from the French National Research Agency (ANR-10-LABX-62-IBEID, ANR-10-LABX-33, INCEPTION project (PIA/ANR-16-CONV-0005)) and from the European Union’s Horizon 2020 research and Innovation Program under grant agrement No 773830 (Project ARDIG, One Health EJP). Pengdbamba Dieudonné Zongo is a scholar of Ed525 CDV, Sorbonne Université, Paris., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018), and Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
- Subjects
Genetics ,0303 health sciences ,030306 microbiology ,Chromosome ,Carbapenemase producing ,Biology ,medicine.disease_cause ,Genome ,3. Good health ,Multiple drug resistance ,03 medical and health sciences ,Plasmid ,medicine ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Clade ,Escherichia coli ,Gene ,030304 developmental biology - Abstract
Carbapenemase-producing Escherichia coli (CP-Ec) represent a major public health threat with a risk of dissemination in the community as it has occurred for lineages producing extended spectrum ß-lactamases. To characterize the extend of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Centre laboratory (F-NRC) for carbapenemase-producing Enterobacterales were investigated. Six hundred and ninety one CP-Ec isolates collected between 2012 and 2015 and 22 before were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex (CC) 23 (ST 410) and CC10 (ST10, ST167) and sporadic isolates including rare ST131 isolates (n=17). However, the most represented ST was ST38 (n=92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n=457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast blaOXA-181 or blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC.IMPORTANCECarbapenemase-producing Escherichia coli (CP-Ec) might be difficult to detect, as minimal inhibitory concentrations can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs. This suggests a still largely uncharacterized community spread of these isolates. Here we have characterized the diversity and evolution of CP-Ec isolated in France before 2016. We show that carbapenemase genes are associated with a wide variety of E. coli genomic backgrounds and a small number of dominant phylogenetic lineages. In a significant proportion of CP-Ec, the most frequent carbapenemase gene blaOXA-48, was detected in isolates lacking any other resistance gene, reflecting the dissemination of pOXA-48 plasmids, likely in the absence of any antibiotic pressure. In contrast carbapenemase gene transfer may also occur in multi-drug resistant E. coli, ultimately giving rise to at-risk lineages encoding carbapenemases with a high potential of dissemination.
- Published
- 2022