Plasmid genomic epidemiology of <i>bla</i> _KPC carbapenemase-producing <i>Enterobacterales</i> in Canada, 2010–2021

Abstract

Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant <i>Enterobacterales</i>, but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. <i>Klebsiella pneumoniae</i> carbapenemase (<i>bla</i>_KPC) is the most common type of carbapenemase in Canada and elsewhere; it can hydrolyze penicillins, cephalosporins, aztreonam, and carbapenems and is frequently found on mobile plasmids in the Tn<i>4401</i> transposon. This means that alongside clonal expansion, <i>bla</i>_KPC can disseminate through plasmid- and transposon-mediated horizontal gene transfer. We applied whole genome sequencing to characterize the molecular epidemiology of 829 <i>bla</i>_KPC carbapenemase-producing isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short-read and long-read sequencing, we obtained 202 complete and circular <i>bla</i>_KPC-encoding plasmids. Using MOB-suite, 10 major plasmid clusters were identified from this data set which represented 87% (175/202) of the Canadian <i>bla</i>_KPC-encoding plasmids. We further estimated the genomic location of incomplete <i>bla</i>_KPC-encoding contigs and predicted a plasmid cluster for 95% (603/635) of these. We identified different patterns of carbapenemase mobilization across Canada related to different plasmid clusters, including clonal transmission of IncF-type plasmids (108/829, 13%) in <i>K. pneumoniae</i> clonal complex 258 and novel repE(pEh60-7) plasmids (44/829, 5%) in <i>Enterobacter hormaechei</i> ST316, and horizontal transmission of IncL/M (142/829, 17%) and IncN-type plasmids (149/829, 18%) across multiple genera. Our findings highlight the diversity of <i>bla</i>_KPC genomic loci and indicate that multiple, distinct plasmid clusters have contributed to <i>bla</i>_KPC spread and persistence in Canada.