Assessment of the Antimicrobial Activity of Cistus salviifolius L. and Helichrysum stoechas (L.) DC Extracts and Their Synergistic Potential with Conventional Antibiotics Against Staphylococcus aureus

This study aimed to evaluate the antibacterial activity of <i>Cistus salviifolius</i> L. and <i>Helichrysum stoechas</i> (L.) DC extracts against <i>S. aureus</i>, including methicillin-resistant <i>S. aureus</i> (MRSA) strains. To this end, assays were conducted to assess killing kinetics, antibiotic combination effects, modulatory effects on ethidium bromide, inhibition of quorum sensing, and biofilm formation. <i>H. stoechas</i> extract demonstrated the strongest activity, with MIC values ranging from 7.8 to 62.5 µg/mL. When combined with antibiotics such as ampicillin, ciprofloxacin, or vancomycin, the extracts of <i>C. salviifolius</i> and <i>H. stoechas</i> predominantly exhibited synergistic (FICI value ≤ 0.5) or additive effects (0.5 < FICI ≤ 1), with some combinations resensitizing resistant strains. The aerial parts of <i>C. salviifolius</i> displayed modulatory effects on ethidium bromide MIC, reducing the concentration from 32 to 8 µg/mL, suggesting efflux pump inhibitory activity. In addition, this extract displayed slight quorum-sensing inhibition at a concentration of 125 µg/mL. Moreover, <i>C. salviifolius</i> and <i>H. stoechas</i> extracts inhibit the formation of biofilm by <i>S. aureus</i> strains, even at subinhibitory concentrations (0.5× and 0.25× MIC). The presence of compounds such as myricetin 3 <i>O</i>-galactoside, catechin derivatives, gallic acid, kaempferol, and chlorogenic acid in the extracts may contribute to their anti-<i>Staphylococcus</i> activity. These results demonstrated the dual antimicrobial and antivirulence potential of <i>C. salviifolius</i> and <i>H. stoechas</i> extracts, highlighting their promise as therapeutic agents or adjuvants against <i>S. aureus.</i> These extracts can be promising candidates for further studies on the development of novel strategies targeting multiple pathogenic pathways.