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

AbstractCarbapenem-resistantEnterobacteriaceaeare considered by WHO as “critical” priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producingEscherichia coli(CP-Ec) in the community is a major public health concern. However, the global molecular epidemiology of CP-Ecisolates, 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 ofEcST410 isolates with a broad analysis of 12,584E. coli and Shigellagenomes, we showed that the fixation of carbapenemase genes depends largely on a combination of mutations inftsIencoding the penicillin binding protein 3 and in the porin genesompCandompF. MutatedftsIgenes and a specificompCallele inducing reduced susceptibility to diverse β-lactams spread across the species by recombination. The selection of CP-Eclineages able to disseminate is more complex than the mere acquisition of carbapenemase genes.