Role of sodium salicylate in Staphylococcus aureus quorum sensing, virulence, biofilm formation and antimicrobial susceptibility

Abstract

The widespread threat of antibiotic resistance requires new treatment options. Disrupting bacterial communication, quorum sensing (QS), has the potential to reduce pathogenesis by decreasing bacterial virulence. The aim of this study was to investigate the influence of sodium salicylate (NaSa) on <i>Staphylococcus aureus</i> QS, virulence production and biofilm formation. In <i>S. aureus</i> ATCC 25923 (<i>agr</i> III), with or without serum, NaSa (10 mM) downregulated the <i>agr</i> QS system and decreased the secretion levels of alpha-hemolysin, staphopain A and delta-hemolysin. Inhibition of <i>agr</i> expression caused a downregulation of delta-hemolysin, decreasing biofilm dispersal and increasing biofilm formation on polystyrene and titanium under static conditions. In contrast, NaSa did not increase biofilm biomass under flow but caused one log₁₀ reduction in biofilm viability on polystyrene pegs, resulting in biofilms being twice as susceptible to rifampicin. A concentration-dependent effect of NaSa was further observed, where high concentrations (10 mM) decreased <i>agr</i> expression, while low concentrations (≤0.1 mM) increased <i>agr</i> expression. In <i>S. aureus</i> 8325-4 (<i>agr</i> I), a high concentration of NaSa (10 mM) decreased <i>hla</i> expression, and a low concentration of NaSa (≤1 mM) increased <i>rnaIII</i> and <i>hla</i> expression. The activity of NaSa on biofilm formation was dependent on <i>agr</i> type and material surface. Eight clinical strains isolated from prosthetic joint infection (PJI) or wound infection belonging to each of the four <i>agr</i> types were evaluated. The four PJI <i>S. aureus</i> strains did not change their biofilm phenotype with NaSa on the clinically relevant titanium surface. Half of the wound strains (<i>agr</i> III and IV) did not change the biofilm phenotype in the 3D collagen wound model. In addition, compared to the control, ATCC 25923 biofilms formed with 10 mM NaSa in the collagen model were more susceptible to silver. It is concluded that NaSa can inhibit QS in <i>S. aureus</i>, decreasing the levels of toxin production with certain modulation of biofilm formation. The effect on biofilm formation was dependent on the strain and material surface. It is suggested that the observed NaSa inhibition of bacterial communication is a potential alternative or adjuvant to traditional antibiotics.