Plasmidomic landscape of Staphylococcus aureus and the emergence of a CC5 subclade harboring the conjugative plasmid pSK41: implications for food safety and antimicrobial resistance.

Staphylococcus aureus can contaminate food products and persist in food-related environments, posing significant challenges to food safety and public health. However, the role of plasmids in mediating antimicrobial resistance (AMR) and facilitating host adaptation in S. aureus has been largely underestimated. We conducted a global plasmidome analysis of 1395 isolates (human: 88.2%, animal: 11.8%) spanning 90 years. Plasmids were detected in 66.8% of strains, typically one to two per genome. We identified 35 distinct plasmid-borne antimicrobial resistance genes (ARGs), with a significant temporal increase in their abundance. Over 85.5% of these plasmids were predicted to be mobilizable, indicating a high transmission potential. Notably, clonal complex 5 (CC5) carried the highest plasmid burden, particularly subclade CC5.6, which exhibited high prevalence of conjugative pSK41 plasmids and ARGs. Although this lineage has not been reported elsewhere, its emergence raises concerns about ARG dissemination through conjugative plasmids. These findings emphasize the role of plasmids in the global spread of AMR and have important implications for food safety and resistance control strategies in food production.