Synergistic Effect of ZnO Nanoparticles and Naringenin on lukE/D Genes Expression in Multidrug-Resistant Staphylococcus aureus.

Multidrug-resistant Staphylococcus aureus (MRSA). This study investigated the antimicrobial efficacy of zinc oxide (ZnO) nanoparticles synthesised through a blue laser-enhanced hydrothermal method combined with the flavonoid Naringenin (NAR) against multidrug-resistant S. aureus isolates. Sixty S. aureus strains were identified using a combination of morphological, biochemical and molecular analyses (VITEK-2 and 16 S rRNA). All strains showed total resistance (100%) to oxacillin and cefoxitin and high resistance levels (60-90%) for vancomycin, erythromycin and fluoroquinolones. Characterization confirmed hexagonal ZNPs with a crystallite size of 38.78 nm. Disk diffusion assays demonstrated enhanced efficacy of ZNPs-NAR combination, achieved a 16.67 mm inhibition zone (p ≤ 0.0001). Notably, while ZNPs singly suppressed leukocidin toxin genes lukD and lukE by 90.3% and 94.9%, inhibition, and NAR reduced expression by 62.4% and 61.9%, the ZNPs-NAR combination showed lower gene suppression (59.3% and 52.8%) yet superior bactericidal activity. This discrepancy reveals that the enhanced bactericidal effect stems not from amplified transcriptional inhibition, but from complementary mechanisms: ZNPs likely disrupt bacterial membranes to facilitate NAR uptake, while NAR concurrently interferes with intracellular targets like DNA replication. The findings demonstrate that nanoparticle-phytochemical combinations can achieve superior antimicrobial effects through synergistic mechanisms, offering a promising strategy to combat multidrug-resistant infections and reduce reliance on conventional antibiotics.