Genomic epidemiology of globalKlebsiella pneumoniaecarbapenemase (KPC)-producingEscherichia coli

ABSTRACTThe dissemination of carbapenem resistance inEscherichia colihas major implications for the management of common human infections.blaKPC,encoding a transmissible carbapenemase (KPC), has historically largely been associated withKlebsiella pneumoniae,a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401,~10kb). Here we characterize the genetic features of the emergence ofblaKPCin globalE. coli,2008-2013, using both long-and short-read whole genome sequencing.Amongst 43/45 successfully sequencedblaKPC-E. colistrains, we identified high strain (n=21 sequence types, 18% of annotated genes in the core genome); plasmid (≥9 replicon types); andblaKPC-associated, mobile genetic element (MGE) diversity (50% not within complete Tn4401elements). We also found evidence of interspecies, regional and international plasmid spread. In several casesblaKPCwas found on high copy number, small Col-like plasmids, previously associated with horizontal transmission of resistance genes in the absence of antimicrobial selection pressures.E. coliis a common human pathogen, but also a commensal in a multiple environmental and animal reservoirs, and easily transmissible. The association ofblaKPCwith a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g.blaTEM,blaCTX-M) suggests that it is likely to become similarly prevalent.