Branger, Catherine, Ledda, Alice, Billard-Pomares, Typhaine, Doublet, Benoît, Fouteau, Stéphanie, Barbe, Valérie, Roche, David, Cruveiller, Stéphane, Edigue, Claudine, Castellanos, Miguel, Decré, Dominique, Drieux-Rouze, Laurence, Clermont, Olivier, Glodt, Jérémy, Tenaillon, Olivier, Cloeckaert, Axel, Arlet, Guillaume, Denamur, Erick, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Service de Microbiologie Clinique [Hôpital Avicenne - APHP], Hôpital Avicenne, Infectiologie Santé Publique (ISP-311), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Laboratoire de Biologie Moléculaire pour l’Etude des Génomes [Evry] (LBioMEG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de biologie François Jacob, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Bactériologie-Hygiène Hospitalière [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], This work was supported by a grant from the Agence Nationale de la Recherche (grant ANR-10-GENM-0012) to C. B. This work was also partially supported by a grant from the ‘Fondation pour la Recherche Médicale to E. D. (Equipe FRM 2016, grant number DEQ20161136698)., Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Centre d'Immunologie et des Maladies Infectieuses (CIMI), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), and MEDIGUE, Claudine
All supporting data, code and protocols have been provided within the article or through supplementary data files. Three supplementary tables are available with the online version of this article.; International audience; To understand the evolutionary dynamics of extended-spectrum b-lactamase (ESBL)-encoding genes in Escherichia coli, we undertook a comparative genomic analysis of 116 whole plasmid sequences of human or animal origin isolated over a period spanning before and after the use of third-generation cephalosporins (3GCs) using a gene-sharing network approach. The plasmids included 82 conjugative, 22 mobilizable and 9 non-transferable plasmids and 3 P-like bacteriophages. ESBL-encoding genes were found on 64 conjugative, 6 mobilizable, 2 non-transferable plasmids and 2 P1-like bacteriophages, indicating that these last three types of mobile elements also play a role, albeit modest, in the diffusion of the ESBLs. The network analysis showed that the plasmids clustered according to their genome backbone type, but not by origin or period of isolation or by antibiotic-resistance type, including type of ESBL-encoding gene. There was no association between the type of plasmid and the phylogenetic history of the parental strains. Finer scale analysis of the more abundant clusters IncF and IncI1 showed that ESBL-encoding plasmids and plasmids isolated before the use of 3GCs had the same diversity and phylogenetic history, and that acquisition of ESBL-encoding genes had occurred during multiple independent events. Moreover, the bla CTX-M-15 gene, unlike other CTX-M genes, was inserted at a hot spot in a bla TEM-1-Tn2 transposon. These findings showed that ESBL-encoding genes have arrived on wide range of pre-existing plasmids and that the successful spread of bla CTX-M-15 seems to be favoured by the presence of well-adapted IncF plasmids that carry a Tn2-bla TEM-1 transposon.