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The dissemination of carbapenemase-producing\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      (CP-\n                      <jats:italic>Ec<\/jats:italic>\n                      ) in the community is a major public health concern. However, the global molecular epidemiology of CP-\n                      <jats:italic>Ec<\/jats:italic>\n                      isolates remains largely unknown as well as factors contributing to the acquisition of carbapenemase genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We first analyzed the whole-genome sequence and the evolution of the\n                      <jats:italic>E. coli<\/jats:italic>\n                      sequence type (ST) 410 and its disseminated clade expressing the carbapenemase OXA-181. We reconstructed the phylogeny of 19\n                      <jats:italic>E. coli<\/jats:italic>\n                      ST enriched in CP-\n                      <jats:italic>Ec<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 13 of the studied STs, acquisition of carbapenemase genes occurred in multidrug-resistant lineages characterized by a combination of mutations in\n                      <jats:italic>ftsI<\/jats:italic>\n                      encoding the penicillin-binding protein 3 and in the porin genes\n                      <jats:italic>ompC<\/jats:italic>\n                      and\n                      <jats:italic>ompF<\/jats:italic>\n                      . Mutated\n                      <jats:italic>ftsI<\/jats:italic>\n                      genes and a specific\n                      <jats:italic>ompC<\/jats:italic>\n                      allele related to that from ST38 inducing reduced susceptibility to diverse \u03b2-lactams spread across the species by recombination. We showed that these mutations precede in most cases the acquisition of a carbapenemase gene. The\n                      <jats:italic>ompC<\/jats:italic>\n                      allele from ST38 might have contributed to the selection of CP-\n                      <jats:italic>Ec<\/jats:italic>\n                      disseminated lineages within this ST. On the other hand, in the pandemic ST131 lineage, CP-\n                      <jats:italic>Ec<\/jats:italic>\n                      were not associated with mutations in\n                      <jats:italic>ompC<\/jats:italic>\n                      or\n                      <jats:italic>ftsI<\/jats:italic>\n                      and show no signs of dissemination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Lineages of CP-\n                      <jats:italic>Ec<\/jats:italic>\n                      have started to disseminate globally. However, their selection is a multistep process involving mutations, recombination, acquisition of antibiotic resistance genes, and selection by \u03b2-lactams from diverse families. This process did not yet occur in the high-risk lineage ST131.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-019-0699-6","type":"journal-article","created":{"date-parts":[[2020,1,19]],"date-time":"2020-01-19T19:02:46Z","timestamp":1579460566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli"],"prefix":"10.1186","volume":"12","author":[{"given":"Rafael","family":"Pati\u00f1o-Navarrete","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Rosinski-Chupin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Cabanel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauraine","family":"Gauthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Takissian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Madec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monzer","family":"Hamze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remy A.","family":"Bonnin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Naas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-2782","authenticated-orcid":false,"given":"Philippe","family":"Glaser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"699_CR1","volume-title":"Tackling drug-resistant infections globally: final report and recommendations: review on antimicrobial resistance","author":"J O\u2019Neill","year":"2016","unstructured":"O\u2019Neill J. 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