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September 22, 2019  |  

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

Authors: Patino-Navarrete, Rafael and Rosinski-Chupin, Isabelle and Cabanel, Nicolas and Gauthier, Lauraine and Takissian, Julie and Madec, Jean-Yves and Hamze, Monzer and Bonnin, Remy A and Naas, Thierry and Glaser, Philippe

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, as well as the genetic bases for the emergence and global dissemination of specific lineages, remain largely unknown. Here, by combining a thorough genomic and evolutionary analysis of Ec ST410 isolates with a broad analysis of 12,398 E. coli and Shigella genomes, we showed that the fixation of carbapenemase genes depends largely on 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 spread across the species by recombination. Those mutations were in most cases selected prior to carbapenemase gene acquisition. The selection of CP-Ec lineages able to disseminate is more complex than the mere acquisition of carbapenemase genes and might be largely triggered by beta-lactams other than carbapenems.

Journal: BioRxiv
DOI: 10.1101/446195
Year: 2018

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