Trans-Regional and Cross-Host Spread of mcr-Carrying Plasmids Revealed by Complete Plasmid Sequences — 44 Countries, 1998−2020

BACKGROUND: The surveillance of antimicrobial resistance genes (ARGs) and bacteria is one critical approach to prevent and control antimicrobial resistance (AMR). Next-generation sequencing (NGS) is a powerful tool in monitoring the emergence and spread of ARGs and resistant bacteria. The horizontal transfer of ARGs across host bacteria mediated by plasmids is a challenge in NGS surveillance for resistance because short-read sequencing can hardly generate the complete plasmid genome sequence, and the correlation between ARGs and plasmids are difficult to determine. METHODS: The complete genome sequences of 455 mcr-carrying plasmids (pMCRs), and the data of their host bacteria and isolation regions were collected from the NCBI database. Genes of Inc types and ARGs were searched for each plasmid. The genome similarity of these plasmids was analyzed by pangenome clustering and genome alignment. RESULTS: A total of 52 Inc types, including a variety of fusion plasmids containing 2 or more Inc types were identified in these pMCRs and carried by complex host bacteria. The cooccurrence of ARGs in pMCRs was generally observed, with an average of 3.9 ARGs per plasmid. Twenty-two clusters with consistent or highly similar sequences and gene compositions were identified by the pangenome clustering, which were characterized with distributions in different countries/regions, years or host bacteria in each cluster. DISCUSSION: Based on the complete plasmid sequences, distribution of mcr genes in different Inc type plasmids, their co-existence with other AMRs, and transmission of one pMCR across regions and host bacteria can be revealed definitively. Complete plasmid genomes and comparisons in the laboratory network are necessary for spread tracing of ARG-carrying plasmids and risk assessment in AMR surveillance.