Correlation of QRDR mutations and MIC levels in fluoroquinolone-resistant <i>Staphylococcus aureus</i> clinical isolates

Antimicrobial resistance is a global health problem. Among various antibiotic-resistant bacteria, <i>Staphylococcus aureus</i>, particularly methicillin-resistant <i>S. aureus</i> (MRSA), is a clinically important pathogen responsible for serious infections because of its multidrug resistance (MDR) and association with high mortality rates. The MDR nature of MRSA, including resistance to macrolides, aminoglycosides, fluoroquinolones, and tetracyclines, limits therapeutic choices and poses significant challenges in clinical management. This study aimed to analyze the correlation between mutations in the quinolone resistance-determining region (QRDR) and the minimum inhibitory concentration (MIC) of fluoroquinolone drugs, such as ciprofloxacin and levofloxacin, in MRSA and methicillin-sensitive <i>S. aureus</i> (MSSA). A total of 63 <i>S</i>. <i>aureus</i> clinical strains were isolated from blood samples of sepsis patients. DNA sequence analysis was performed using gDNA extracted from all <i>S. aureus</i> clinical isolates to identify mutations in the QRDR of <i>gyr</i>A, <i>gyr</i>B, <i>par</i>C, and <i>par</i>E. The MICs of antimicrobials were determined by the broth microdilution method. Among these genes, only mutations in <i>par</i>C showed a statistically significant positive correlation with elevated MIC levels, underscoring the primary role of <i>par</i>C in mediating resistance in our clinical isolates. Notably, all isolates exhibited a substitution at serine 80 (S80) in <i>par</i>C, and those harboring simultaneous substitutions at both S80 and glutamic acid 84 (E84) demonstrated markedly increased MIC values for both drugs. These findings reinforce previously reported associations between dual mutations and high-level fluoroquinolone resistance, while highlighting the distinct contribution of <i>par</i>C among the QRDR genes analyzed in this study. Furthermore, we found that the most frequent mutation in the QRDR was the cytosine-to-thymine mutation.IMPORTANCEAntimicrobial resistance is a growing global health crisis, making bacterial infections harder to treat. <i>Staphylococcus aureus</i>, especially MRSA, is a major concern due to its resistance to multiple antibiotics, including fluoroquinolones like ciprofloxacin and levofloxacin. Our study highlights how specific genetic mutations in the quinolone resistance-determining region (QRDR) influence fluoroquinolone resistance. We found that mutations in the <i>par</i>C gene, particularly substitutions at serine 80 (S80) and glutamic acid 84 (E84), significantly increase resistance. Understanding these mutations helps predict antibiotic resistance and may guide more effective treatment strategies. By identifying key genetic changes that drive fluoroquinolone resistance, our research contributes to developing improved diagnostic tools and targeted therapies to combat drug-resistant <i>S. aureus</i> infections. This knowledge is crucial for clinicians and researchers working to control the spread of antibiotic-resistant bacteria and improve patient outcomes.