Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 18 5 2026 10 05 729 740 Sahar Milani Department of Medical Microbiology, Yasuj University of Medical Sciences, Yasuj, Iran Hadi Ebrahimi Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran Seyed Sajjad Khoramrooz Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran Leila Manzuri Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran Marjan Salahi Department of Medical Microbiology, Yasuj University of Medical Sciences, Yasuj, Iran Seyed Abdolmajid Khosravani Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran Kasra Sharifi Student Research Committee, Kazerun Branch, Islamic Azad University, Kazerun, Iran Asghar Sharifi Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran 2026 05 28 2026 09 20 Background and Objectives: Staphylococcus aureus poses clinical challenges through its virulence and antibiotic resistance, including SCCmec-mediated methicillin resistance. Integrated data on virulence profiling, molecular typing, and resistance are limited in Southwest Iran. We characterized virulence genes, SCCmec types, integrons, and antimicrobial resistance in S. aureus from diverse clinical sources in Yasuj, Iran. Materials and Methods: We analyzed 214 S. aureus isolates recovered from tonsil, wound, sinus, and blood specimens (2020–2023). Species confirmation was by nuc PCR. Antimicrobial susceptibility testing followed CLSI disk diffusion guidelines; MRSA was confirmed by mecA PCR. PCR assays detected hemolysin genes (hla, hlb, hld), toxin genes (tst, pvl, eta, etb, etd), MSCRAMM genes (sdrC, sdrD, sdrE), sak, integrase genes (intI, intII), and SCCmec types I, III, and IVa. Results: Isolates were from tonsils (59.8%), wounds (29.9%), sinusitis (6.1%), and blood (4.2%). MRSA prevalence was 29.0%. Highest resistance was to penicillin (98.6%), erythromycin (59.3%), and tetracycline (54.7%), with MDR in 32.7%. Prevalent virulence genes were hld (87.9%), hla (68.2%), sak (60.3%), sdrC (44.4%), eta (37.9%), sdrD (36.9%), tst (32.2%), sdrE (29.0%), etd (18.2%), and pvl (3.7%). Among 104 MDR/MRSA isolates, intI and intII were found in 14.4% and 10.6%. SCCmec type III dominated (80.5%), followed by I (14.5%) and IVa (5.0%); types I and III were significantly linked to MDR (P < 0.05). Four isolates co-harbored pvl, tst, and hla. Conclusion: Considerable virulence gene carriage and SCCmec type III dominance were observed. Gentamicin, ciprofloxacin, cotrimoxazole, and clindamycin remain effective. Coexistence of life-threatening toxin genes and high resistance rates necessitates enhanced infection control. https://ijm.tums.ac.ir/index.php/ijm/article/view/6223 https://ijm.tums.ac.ir/index.php/ijm/article/download/6223/1934