Global transmission network and driving mechanisms: An epidemiological and genomic study of bla OXA -mcr co-carrying strains

Purpose The co-carriage of carbapenem-resistant bla _OXA genes and colistin-resistant mcr genes in bacterial strains represents a critical threat to public health by undermining last-resort antibiotics. This study aims to systematically investigate the global prevalence, transmission dynamics, and genetic drivers of bla _OXA - mcr co-carrying strains to inform surveillance and intervention strategies. Methods We conducted a comprehensive analysis of 3,665 bacterial genomes from the NCBI database (1953–2024), identifying 284 bla _OXA - mcr co-carrying strains. Using bioinformatics tools, we characterized their spatiotemporal distribution, phylogenetic relationships, plasmid environments, and mobile genetic element (MGE) structures. Results The 284 strains were isolated from 30 countries, with Germany showing the highest detection rate (47.2%). The dominant genotype combination was bla _OXA−48 – mcr-10 (74.3%), primarily carried by Enterobacteriaceae. Phylogenetic analysis confirmed transcontinental and cross-host transmission events, including a Romania–UK clone differing by only one SNP. The species composition shifted from Acinetobacter baumannii to Enterobacteriaceae, and the host spectrum expanded to include pets and environmental samples after 2016. bla _OXA genes were predominantly plasmid-borne (66.9%), mainly on IncL plasmids, while mcr genes were frequently located on IncHI2A plasmids. Notably, flanking MGE structures exhibited a trend toward simplification, potentially reducing fitness costs. Conclusion bla _OXA - mcr co-carrying strains have formed a complex global transmission network transcending national, species, and host barriers, driven by synergistic plasmid–clone co-evolution. These findings underscore the urgent need for proactive One Health surveillance and targeted interventions to mitigate the spread of these dual last-resort resistant pathogens.