Step by step evolution and convergent recombination shape the global dissemination of carbapenamase expressing Escherichia coli clones.

Carbapenemase resistant Enterobacteriaceae are considered by WHO as a “critical” priority and among them Escherichia coli is the most frequent pathogen responsible for both community and hospital acquired infections. The dissemination of carbapenemase producing E. coli (CP-Ec) in the community is a major threat. However, the global molecular epidemiology of CP-Ec strains remains largely unknown as well as the genetic bases for the emergence and global dissemination of specific lineages. Here by combining a thorough genomic and evolutionary analysis of ST410 strains and a broad analysis of E. coli genomes we showed that the fixation of carbapenemase genes depends largely on a combination of mutations in ftsI encoding PBP3 and in the porin genes ompC and ompF. Mutated ftsI genes and of a specific ompC allele spread across the species by recombination. Those mutations were in most cases selected prior to carbapenemase acquisition. The selection of CP-Ec lineages able to disseminate is more complex than only the acquisition of a carbapenemase gene and might be largely triggered by other ?-lactams than carbapenems.