Genomic epidemiology of globalKlebsiella pneumoniaecarbapenemase (KPC)-producingEscherichia coli
Stoesser N., Sheppard AE., Peirano G., Anson LW., Pankhurst L., Sebra R., Phan HTT., Kasarskis A., Mathers AJ., Peto TEA., Brandford P., Motyl MR., Walker AS., Crook DW., Pitout JD.
ABSTRACT The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common human 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, ~10kb). Here we characterize the genetic features of the emergence of bla KPC 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 high strain (n=21 sequence types, 18% of annotated genes in the core genome); plasmid (≥9 replicon types); and bla KPC -associated, mobile genetic element (MGE) diversity (50% not within complete Tn 4401 elements). We also found evidence of interspecies, 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 a 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 T EM , bla CTX-M ) suggests that it is likely to become similarly prevalent.