Jenny Szeto, Rhys T. White, Hermes Pérez, Allan J. Hardaker, Kristin Dyet, Juliet Elvy, Simon Jackson, Rose M. Collis, Adrian L. Cookson, Clint Gray, Imogen Skelton, William Taylor, Isabelle Pattis, Zuyu Yang
OBJECTIVES: Characterize plasmid backbones and mobility contexts of mobile colistin resistance in clinical bacteria from New Zealand and place them within a global framework. METHODS: We sequenced 71 mcr-positive isolates (42 with nanopore reads) and curated 1543 mcr-bearing plasmids. Pangenome clustering, mcr phylogeny, and mapping of insertion sequences and antimicrobial resistance cargo resolved plasmid backbone lineages and dissemination patterns. RESULTS: New Zealand isolates carried five of the twelve mcr genes (mcr-1 to mcr-12) across Escherichia coli, Enterobacter spp., Klebsiella spp., and Citrobacter spp. mcr-1, mcr-3, and mcr-8 isolates were colistin non-susceptible; most mcr-9 remained susceptible with occasional heteroresistance suggested by skip-well growth, whereas most mcr-10 were non-susceptible with frequent heteroresistance. Nanopore sequencing produced 42/42 complete chromosomes and 112/119 circular plasmids. Globally, 1543 mcr-carrying plasmids (1984-2024) from 60 countries and regions were identified from human and animal isolates, as well as environmental, food, and unknown sources. Pangenome clustering resolved 14 plasmid lineages associated with mcr variants, replicon backbones, and host range. We detected 18 single-Inc and 58 multi-Inc combinations, with mcr-1 mainly on IncI2/IncX4/IncHI2A, mcr-9 on IncHI2A, mcr-3 on IncC and F-type, and mcr-8/mcr-10 on F-type. Insertion sequence (IS) analysis revealed 56 mobility configurations dominated by IS30, IS5, and IS6. About 40% of plasmids lacked flanking IS, and co-carriage of other antimicrobial resistance genes was common. CONCLUSIONS: In New Zealand, mcr dynamics are shaped by transmissible plasmid backbones and multidrug co-selection, mirroring global trends. This genome-resolved, four-decade plasmid framework clarifies mcr evolution and supports a backbone-focused approach to surveillance.