Genomic diversity and antimicrobial resistance ofStaphylococcus aureus in Saudi Arabia: a nationwide studyusing whole-genome sequencing

Methicillin-resistant Staphylococcus aureus (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 remains limited. Here, we present an integrated analysis of S. aureus isolates collected across seven Saudi Arabian regions, combining whole-genome sequencing with extensive antimicrobial susceptibility testing and standardized metadata following FAIR data principles. Our analysis revealed striking differences between pilgrimage and non-pilgrimage cities. Pilgrimage cities showed significantly higher genetic diversity and antimicrobial resistance rates, harboring numerous international strains including recognized clones from diverse geographic origins. Reported lineage dynamics is 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, highlighting 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. ImportanceGenomic data enables the tracking of pathogens by revealing clonal expansions within populations and identifying successful lineages. However, comprehensive national-level data from Saudi Arabia remains limited on a large scale. The adoption of FAIR principles and reproducible workflows ensures robust, consistent analysis, fostering effective data sharing. The OneHealth approachs success depends on the integration and collaboration across diverse domains in todays digital landscape.