{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Patino-Navarrete R"],"funding":["Agence Nationale de la Recherche","H2020 European Institute of Innovation and Technology"],"pagination":["10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6970295"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Lineages of CP-Ec have started to disseminate globally. However, their selection is a multistep process involving mutations, recombination, acquisition of antibiotic resistance genes, and selection by β-lactams from diverse families. This process did not yet occur in the high-risk lineage ST131."],"journal":["Genome medicine"],"pubmed_title":["Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli."],"pmcid":["PMC6970295"],"funding_grant_id":["ANR-10-LABX-33","ANR-14-JAMR-0002","Labex IBEID","773830  (ARDIG)"],"pubmed_authors":["Patino-Navarrete R","Hamze M","Rosinski-Chupin I","Takissian J","Cabanel N","Naas T","Madec JY","Glaser P","Gauthier L","Bonnin RA"],"additional_accession":[]},"is_claimable":false,"name":"Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli.","description":"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Lineages of CP-Ec have started to disseminate globally. However, their selection is a multistep process involving mutations, recombination, acquisition of antibiotic resistance genes, and selection by β-lactams from diverse families. This process did not yet occur in the high-risk lineage ST131.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2024-10-18T05:21:07.772Z","creation":"2020-05-22T08:30:30Z"},"accession":"S-EPMC6970295","cross_references":{"pubmed":["31955713"],"doi":["10.1186/s13073-019-0699-6"]}}