Genomic and epidemiological insights into the emergence and dominance of MRSA clones in Riyadh's healthcare facilities.

The emergence and expansion of methicillin-resistant Staphylococcus aureus (MRSA) clones in healthcare facilities pose a significant public health concern due to their adaptability and resistance to commonly used antibiotics. In this study, the genomic and epidemiological characteristics of 81 MRSA isolates collected between February and June 2022 were analyzed. ST5 (25.9%) and ST6 (19.7%) emerged as the dominant sequence types, collectively accounting for 45.6% of infections. Whole-genome sequencing and phenotypic analyses revealed that ST5 clone exhibited a broader multidrug-resistant profile compared to ST6 clone, with higher prevalence of β-lactam, tetracycline, and trimethoprim resistance. ST6 clone showed more variable resistance, including aminoglycoside and macrolide genes, suggesting a possible community origin before adaptation to hospital settings. Phylogenetic analysis demonstrated ongoing microevolution within Clonal Complex 5 (CC5), including the identification of novel single-locus variants such as ST8111. Correlation analyses highlighted significant associations between key resistance genes and their phenotypic profiles, reflecting complex co-resistance mechanisms. Additionally, virulence profiling revealed that ST5 uniquely carried tsst-1, whereas PVL genes were absent in both ST5 and ST6 and appeared only in a small subset of other MRSA clones. The emergence of highly resistant clones like ST672 underscores the potential concern for sustained genomic surveillance. The observed clonal shift from ST239 to ST5 and ST6 signals a dynamic MRSA landscape in Saudi Arabia, emphasizing the need for integrated molecular epidemiology and targeted infection control strategies.