title: IS1R-mediated plasticity of IncL/M plasmids leads to the insertion of bla OXA-48 into the Escherichia coli Chromosome.
abstract: The OXA-48 carbapenemase is mainly encoded by ∼ 62-kb IncL/M plasmids. However, chromosome-mediated genes have been observed in Escherichia coli isolates. In this work, we investigated the genetic environment of OXA-48 in members of the family Enterobacteriaceae (n = 22) to understand how the OXA-48-encoding gene is transferred into the E. coli chromosome. The OXA-48-encoding gene was located within intact Tn1999.2 transposons in the ∼ 62-kb plasmids or within a truncated variant of Tn1999.2 for the OXA-48-encoding genes located in the chromosomes of E. coli bacteria. The analysis of the Tn1999.2 genetic environment revealed an inverted orientation of the transposon in five ∼ 62-kb plasmids (5/14 [35%]) and in all chromosome inserts (n = 8). The sequencing of pRA35 plasmid showed that this orientation of Tn1999.2 and the acquisition of an IS1R insertion sequence generated a 21.9-kb IS1R-based composite transposon encoding OXA-48 and designated Tn6237. The sequencing of a chromosomal insert encoding OXA-48 also revealed this new transposon in the E. coli chromosome. PCR mapping showed the presence of this element in all strains harboring an OXA-48-encoding chromosomal insert. However, different insertion sites of this transposon were observed in the E. coli chromosome. Overall, these findings indicate a plasticity of the OXA-48 genetic environment mediated by IS1R insertion sequences. The insertion sequences can induce the transfer of the OXA-encoding gene into E. coli chromosomes and thereby promote its persistence and expression at low levels.
authors.affiliation: Clermont Université, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France Health and Environment Microbiology Laboratory, AZM Research Centre of Biotechnology, Doctoral School of Sciences and Technology, and Faculty of Public Health, Lebanese University, Tripoli, Lebanon Centre Hospitalier Universitaire, Clermont-Ferrand, France.
authors.forename: R
authors.initials: R
authors.lastname: Beyrouthy
authors.affiliation: Clermont Université, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France Centre Hospitalier Universitaire, Clermont-Ferrand, France.
authors.forename: F
authors.initials: F
authors.lastname: Robin
authors.affiliation: Clermont Université, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France Centre Hospitalier Universitaire, Clermont-Ferrand, France.
authors.forename: J
authors.initials: J
authors.lastname: Delmas
authors.affiliation: Clermont Université, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France Centre Hospitalier Universitaire, Clermont-Ferrand, France.
authors.forename: L
authors.initials: L
authors.lastname: Gibold
authors.affiliation: Clermont Université, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France.
authors.forename: G
authors.initials: G
authors.lastname: Dalmasso
authors.affiliation: Health and Environment Microbiology Laboratory, AZM Research Centre of Biotechnology, Doctoral School of Sciences and Technology, and Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
authors.forename: F
authors.initials: F
authors.lastname: Dabboussi
authors.affiliation: Health and Environment Microbiology Laboratory, AZM Research Centre of Biotechnology, Doctoral School of Sciences and Technology, and Faculty of Public Health, Lebanese University, Tripoli, Lebanon.
authors.forename: M
authors.initials: M
authors.lastname: Hamzé
authors.affiliation: Clermont Université, UMR 1071 INSERM/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France Centre Hospitalier Universitaire, Clermont-Ferrand, France rbonnet@chu-clermontferrand.fr.
authors.forename: R
authors.initials: R
authors.lastname: Bonnet
mesh_terms: D002876:Chromosomes, Bacterial / Q000235:genetics*; D019295:Computational Biology; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics*; D016254:Mutagenesis, Insertional; D010957:Plasmids / Q000235:genetics*; D016133:Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D004254:DNA Nucleotidyltransferases; C069595:IS1 recombinase; D001618:beta-Lactamases; C000601047:beta-lactamase OXA-48, E coli; C108449:oxacillinase
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