| Summary: | In this study, we investigated both meat-derived and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), exploring their genetic relatedness to patient-derived MRSA isolates in Saudi Arabia. We collected 250 meat samples and identified 53 <i>S. aureus</i> isolates, with 79% being methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA) and 21% being MRSA. Moreover, we included 80 clinically confirmed patient-derived MRSA isolates. We identified the most common <i>S. aureus</i> clone in both patients and retail meat. In meat, ST6 and ST97 were the most common clones in 55% of the MRSA isolates, and ST1153 and ST672 were the most common in 21% and 17% of the MSSA isolates. In patients, ST5 and ST6 were the predominant clones in 46% of the <i>S. aureus</i> isolates. CC5/ST5-SCCmecVc-t311 and CC361/ST672-SCCmecV-t3841 were common MRSA clones in both meat and patients. CC97 and CC361 clones were the second most prevalent <i>S. aureus</i> clones in meat and were relatively common in patients. Furthermore, we sequenced and characterized novel <i>S. aureus</i> strains ST8109, ST8110, and ST8111. The genomic similarities between meat- and patient-derived <i>S. aureus</i> isolates suggest that retail meat might be a reservoir for <i>S.aureus</i> and MRSA transmission. Therefore, a structured One Health approach is recommended for <i>S. aureus</i> dissemination, genetic characterization, antibiotic resistance, and impact on human health.
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