Genomic analysis elucidates characteristics and possible origins of high-risk antimicrobial resistance genes in from a global perspective.

Under the One Health framework, it is crucial to undertake a comprehensive analysis of antimicrobial resistance (AMR) across various countries and regions. High-risk ARGs pose a severe threat to human health, yet systematic research on them is scarce. This study developed a high-risk ARGs database using the existing risk assessment system and explored a genome-based investigation workflow for high-risk ARGs. We investigated , a common clinical pathogen, to understand the epidemiological characteristics of high-risk ARGs, including their primary sources and destinations. Results revealed that high-risk ARGs are widespread in , with being the most abundant and the most widely distributed. The combination of vancomycin_ARGs (, , , ) -- is the most prevalent. ST1579 harbors the most high-risk ARGs, and the top five STs carrying high-risk ARGs are all from the hospital-specific CC17 clone lineage (cladeA1). Similarly, , , and vancomycin_ARGs-positive strains also belong to the nosocomial infection-related lineage cladeA1. Oxazolidinones_ARGs (, , )-positive strains are mainly from the cladeA2 lineage associated with animals. , a last-resort antibiotics ARG with potential outbreak risk, requires particular attention. Additionally, plasmids, transposons (Tn), Insertion sequence (IS), and integrative conjugative elements (ICE) show varying preferences for encoding high-risk ARGs, with , , , , , and being more readily carried by these MGEs. The USA, China, and Belgium are key origin regions for high-risk ARGs in , while Australia, France and Netherlands are significant introduction regions. This study provides essential data for tackling the global AMR crisis.