Genomic diversity and antimicrobial resistance of Staphylococcus aureus in Saudi Arabia: a nationwide study using whole-genome sequencing

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) surveillance in regions with mass gatherings presents unique challenges for public health systems. Saudi Arabia, hosting millions of pilgrims annually, provides a distinctive setting for studying how human mobility shapes bacterial populations, yet comprehensive genomic surveillance data from this region remain limited. Here, we present an integrated analysis of <i>S. aureus</i> isolates collected across seven Saudi Arabian regions, combining whole-genome sequencing with extensive antimicrobial susceptibility testing and standardized metadata following findability, accessibility, interoperability and reusability data principles. Our analysis revealed striking differences between pilgrimage and non-pilgrimage cities. Pilgrimage cities showed significantly higher genetic diversity and antimicrobial resistance rates, harbouring numerous international strains, including recognized clones from diverse geographic origins. Reported lineage dynamics are changing, expanding toward community clones. While genomic prediction of antimicrobial resistance showed high accuracy for some antibiotics, particularly beta-lactams, with varying performance for others, it highlights the necessity for phenotypic testing in clinical settings. Our findings demonstrate how mass gatherings drive bacterial population structures and emphasize the importance of integrated surveillance approaches in regions with significant global connectivity and travel.