Plasmid genomic epidemiology of carbapenem-hydrolysing class D β-lactamase (CDHL)-producing in Canada, 2010-2021.

Carbapenems are last-resort antibiotics for treatment of infections caused by multidrug-resistant , but carbapenem resistance is a rising global threat due to the acquisition of carbapenemase genes. Oxacillinase-48 ( )-type carbapenemases are increasing in abundance in Canada and elsewhere; these genes are frequently found on mobile genetic elements and are associated with specific transposons. This means that alongside clonal dissemination, genes can spread through plasmid-mediated horizontal gene transfer. We applied whole genome sequencing to characterize 249 -producing isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short- and long-read sequencing, we obtained 70 complete and circular -encoding plasmids. Using MOB-suite, four major plasmids clustered were identified, and we further estimated a plasmid cluster for 91.9 % (147/160) of incomplete -encoding contigs. We identified different patterns of carbapenemase mobilization across Canada, including horizontal transmission of /IncX3 plasmids (75/249, 30.1 %) and /IncL/M plasmids (47/249, 18.9 %), and both horizontal transmission and clonal transmission of for ST231 on ColE2-type/ColKP3 plasmids (25/249, 10.0 %). Our findings highlight the diversity of OXA-48-type plasmids and indicate that multiple plasmid clusters and clonal transmission have contributed to spread and persistence in Canada.