Abstract
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 Enterococcus faecium, 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 E. faecium, with tet(M) being the most abundant and ermB the most widely distributed. The combination of vancomycin_ARGs (vanA, vanYA, vanYB, vanYM) -tet(M)-ermB 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, tet(M)-, ermB-, and vancomycin_ARGs-positive strains also belong to the nosocomial infection-related lineage cladeA1. Oxazolidinones_ARGs (optrA, cfr(D), cfrA)-positive strains are mainly from the cladeA2 lineage associated with animals. OptrA, 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 tet(M), ermB, APH (3 ')-IIIa, vanA, vanYA, and vanYB being more readily carried by these MGEs. The USA, China, and Belgium are key origin regions for high-risk ARGs in E. faecium, while Australia, France and Netherlands are significant introduction regions. This study provides essential data for tackling the global AMR crisis.