Genomic epidemiology of global Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli

The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common infections. blaKPC, encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401, ~10kb). Here we characterize the genetic features of blaKPC emergence in global E. coli, 2008-2013, using both long- and short-read whole-genome sequencing. Amongst 43/45 successfully sequenced blaKPC-E. coli strains, we identified substantial strain diversity (n=21 sequence types, 18% of annotated genes in the core genome); substantial plasmid diversity (≥9 replicon types); and substantial blaKPC-associated, mobile genetic element (MGE) diversity (50% not within complete Tn4401 elements). We also found evidence of inter-species, regional and international plasmid spread. In several cases blaKPC was 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. coli is a common human pathogen, but also a commensal in multiple environmental and animal reservoirs, and easily transmissible. The association of blaKPC with a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g. blaTEM, blaCTX-M) suggests that it may become similarly prevalent.</p