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Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli

Abstract : Background: Carbapenem-resistant Enterobacteriaceae are considered by WHO as "critical" priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producing Escherichia coli (CP-Ec) in the community is a major public health concern. However, the global molecular epidemiology of CP-Ec isolates remains largely unknown as well as factors contributing to the acquisition of carbapenemase genes. Methods: We first analyzed the whole-genome sequence and the evolution of the E. coli sequence type (ST) 410 and its disseminated clade expressing the carbapenemase OXA-181. We reconstructed the phylogeny of 19 E. coli ST enriched in CP-Ec and corresponding to a total of 2026 non-redundant isolates. Using the EpiCs software, we determined the significance of the association between specific mutations and the acquisition of a carbapenemase gene and the most probable order of events. The impact of the identified mutations was assessed experimentally by genetic manipulations and phenotypic testing. Results: In 13 of the studied STs, acquisition of carbapenemase genes occurred in multidrug-resistant lineages characterized by a combination of mutations in ftsI encoding the penicillin-binding protein 3 and in the porin genes ompC and ompF. Mutated ftsI genes and a specific ompC allele related to that from ST38 inducing reduced susceptibility to diverse β-lactams spread across the species by recombination. We showed that these mutations precede in most cases the acquisition of a carbapenemase gene. The ompC allele from ST38 might have contributed to the selection of CP-Ec disseminated lineages within this ST. On the other hand, in the pandemic ST131 lineage, CP-Ec were not associated with mutations in ompC or ftsI and show no signs of dissemination.
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Submitted on : Wednesday, May 6, 2020 - 12:44:39 PM
Last modification on : Thursday, November 17, 2022 - 3:36:55 AM


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Rafael Patino-Navarrete, Isabelle Rosinski-Chupin, Nicolas Cabanel, Lauraine Gauthier, Julie Takissian, et al.. Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli. Genome Medicine, 2020, 12, pp.10. ⟨10.1186/s13073-019-0699-6⟩. ⟨pasteur-02565307⟩



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