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. bla KPC , encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae , a predominant plasmid (pKpQIL), and a specific transposable element (Tn 4401 , ~10 kb). Here we characterize the genetic features of bla KPC emergence in global E. coli , 2008–2013, using both long- and short-read whole-genome sequencing. Amongst 43/45 successfully sequenced bla KPC - 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 bla KPC -associated, mobile genetic element (MGE) diversity (50% not within complete Tn 4401 elements). We also found evidence of inter-species, regional and international plasmid spread. In several cases bla KPC 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 bla KPC with a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g. bla TEM , bla CTX-M ) suggests that it may become similarly prevalent.