Genomic insights into the tmexCD-toprJ : plasmid-mediated evolution, dissemination and diversity in bacterial populations

BACKGROUND: The plasmid-mediated tigecycline resistance gene tmexCD-toprJ has emerged in clinical and animal isolates, but its epidemiological spread and plasmid adaptation mechanisms remain unclear. METHODS: We characterized tmexCD-toprJ-carrying plasmids from the PLSDB database through comprehensive bioinformatic analyses, revealing their genetic features and potential inter-species transmission routes. RESULTS: Genomic analysis of 197 tmexCD-toprJ-carrying plasmids revealed significant backbone diversity, clustering into 18 groups and 12 singletons. The 30 identified host species were predominantly Klebsiella pneumoniae (K. pneumoniae) (53.3%), followed by Pseudomonas aeruginosa (P. aeruginosa) (16.8%) and Klebsiella quasipneumoniae (K. quasipneumoniae) (4.1%). MOB-suite typing classified 53.8% as conjugative, 5.6% mobilizable and 40.61% non-mobilizable. Over half of the tmexCD-toprJ-carrying plasmids were predicted to contain the MOBH family. Among the identified variants, tmexCD1-toprJ1, tmexCD2-toprJ2 and tmexCD3-toprJ1 representing the predominant forms. TmexCD1-toprJ1 was linked to IncFIB/IncHI1B/rep_cluster_1254 plasmids, while tmexCD2-toprJ2 associated with diverse replicons, enabling cross-species spread. A total of 14 plasmids co-localized tmexCD-toprJ with carbapenemase (blaNDM/KPC) and mcr genes, forming high-risk resistance platforms. Notably, a 36 483 bp insertion in IncP/rep_cluster_1115 plasmids disrupted tmexC6D6-toprJ1b and carried heavy metal resistance genes. CONCLUSIONS: These findings enhance our understanding of the diversity of tmexCD-toprJ-carrying plasmids. The convergence of tmexCD-toprJ with carbapenemase and polymyxin resistance genes in clinically prevalent plasmids underscores an urgent need for enhanced surveillance targeting complete genetic environments.