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 (Tn4401, ∼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 Tn4401 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.