Synergistic effect of antibiotics, α-linolenic acid and solvent type against Staphylococcus aureus biofilm formation

BACKGROUND: A promising approach to the treatment of bacterial infections involves inhibiting the quorum sensing (QS) mechanism to prevent the formation and growth of bacterial biofilm. While antibiotics are used to kill remaining bacteria, QS inhibitors (QSIs) allow for antibiotic doses to be reduced. This study focuses on evaluating the synergy between gentamicin sulphate (GEN), tobramycin (TOB), or azithromycin (AZM) with linolenic acid (LNA) against the formation of an early Staphylococcus aureus biofilm. METHODS: Minimum biofilm inhibitory concentration (MBIC) was determined using the resazurin reduction assay for all antibiotics and LNA. The reduction of biofilm mass was assessed using the crystal violet (CV) assay. We have also evaluated the effect of dimethyl sulfoxide with TWEEN (DMSOT) on early biofilm formation. Synergy was determined by metabolic activity assay and fractional biofilm inhibitory concentration (FBIC). RESULTS: DMSOT at a concentration of 1% enhanced early biofilm formation, but also decreased the doses of antibiotic needed to reduce the biofilm by up to 8 times. Adding LNA at a concentration of 32 µg/ml or 64 µg/ml allowed up to a 32-fold reduction of antibiotic doses for GEN and TOB and a 4-fold reduction for AZM. CONCLUSIONS: LNA's use in combination with various antibiotics could reduce their doses and help fight drug-resistant bacteria in the biofilm.