Antibacterial and resistance-modifying activities of thymoquinone against oral pathogens

Background: The presence of resistant bacteria in the oral cavity can be the major cause of dental antibiotic prophylaxis failure. Multidrug efflux has been described for many organisms, including bacteria and fungi as part of their drugs resistance strategy. The discovery of a new efflux pump inhibitor could extend the useful lifetime of some antibiotics. Methods: In this study, the MICs of thymoquinone (TQ), tetracycline and benzalkonium chloride (BC) were determined in absence and in presence of a sub-MIC doses of thymoquinone (1/2 MIC). In addition the 4,6-diamidino-2-phenylindole (DAPI) efflux assay was carried out to determine the effect of TQ on DAPI cells accumulation. Results: TQ induced a selective antimicrobial activity. Its synergic effect resulted in at least a 4-fold potentiation of the tested antibiotics and antiseptic. In addition, TQ inhibited the DAPI efflux activity in a concentration-dependent manner. The rate of DAPI accumulation in clinical isolates was enhanced with TQ (0 to 200 mu g/ml). There is also a decrease in loss of DAPI from bacteria in the presence of TQ. The concentration causing 50% of DAPI efflux inhibition after 15 minutes was approximately 59 mu g/ml for Pseudomonas aeroginosa and 100 mu g/ml and Staphylococcus aureus respectively. Conclusions: TQ possesses a selective antibacterial activity against oral bacteria. It is therefore suggested that TQ could be used as a source of natural products with resistance-modifying activity. Further investigation is needed to assess their clinical relevance.