Plasmid Genomic Epidemiology of Carbapenemase-producing in Canada, 2010-2021

Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant , but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. carbapenemase () 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 transposon. This means that alongside clonal expansion, can disseminate through plasmid- and transposon-mediated horizontal gene transfer. We applied whole genome sequencing to characterize the molecular epidemiology of 829 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 -encoding plasmids. Using MOB-suite, 10 major plasmid clusters were identified from this data set which represented 87% (175/202) of the Canadian -encoding plasmids. We further estimated the genomic location of incomplete -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 clonal complex 258 and novel repE(pEh60-7) plasmids (44/829, 5%) in 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 genomic loci and indicate that multiple, distinct plasmid clusters have contributed to spread and persistence in Canada.