Effect of terpinolene against the resistant Staphylococcus aureus strain, carrier of the efflux pump QacC and β-lactamase gene, and its toxicity in the Drosophila melanogaster model.

Efflux pumps and β-lactamases are mechanisms of bacterial resistance that exist in Staphylococcus aureus , where both mechanisms are expressed simultaneously in the SA K4100 strain, with its efflux pump being characterized as QacC (Quaternary Ammonium Compounds C). The search for inhibitors of these mechanisms has grown gradually, with research on isolated compounds, including terpenes, which have innumerable biological activities, being common. This study sought to evaluate the antibacterial activity of Terpinolene against the S. aureus K4100 strain, carrying a QacC efflux pump and β-lactamase, as well as to evaluate its toxicity in the Drosophila melanogaster arthropod model. Determination of the Minimum Inhibitory Concentration (MIC) was performed by broth microdilution. Efflux pump inhibition was evaluated by the MIC reduction of Oxacillin and Ethidium Bromide (EtBr). β-Lactamase inhibition was analyzed by the MIC reduction of Ampicillin with Sulbactam. Toxicity was verified by mortality parameters and locomotor assays in D. melanogaster. The results demonstrated that Terpinolene did not present a direct antibacterial activity (MIC ≥ 1024 μg/mL). However, a reduction in MIC was observed when Terpinolene was associated with Oxacillin (161.26–71.83 μg/mL) and EtBr (45.25–32 μg/mL), possibly by a β-lactamase and efflux pump inhibition, thus evidencing a modulatory activity. Terpinolene presented D. melanogaster mortality with an EC 50 of 34.6 μL/L within 12 h of exposure. Additionally, Terpinolene presented damage to the locomotor system after the second hour of exposure, with the effect increasing in a concentration-dependent manner. In conclusion, new tests should be carried out to investigate the Terpinolene reinforcement of antibiotic activity and toxic activity mechanisms of action. • Terpinolene may be able to inhibit efflux pumps in association whit antibiotics; • Terpinolene combined with antibiotics may be able to inhibit β-lactamases; • Terpinolene with Ethidium Bromide decrease Minimum Inhibitory Concentration; • Terpinolene demonstrates to be toxic against Drosophila melanogaster ; • Terpinolene presentes damage to the locomotor apparatus of Drosophila melanogaster. [ABSTRACT FROM AUTHOR]