Study on Demethoxycurcumin as a promising approach to reverse methicillin-resistance of Staphylococcus aureus

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) has always been a thorny pathogen, posing serious threat to public health. Current treatment resort for MRSA infections is still scarce. Research on phytochemical component that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigating the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and exploring its possible mechanism for eliminating MRSA resistance. Methods The present study determined minimum inhibitory concentrations (MICs) of DMC, oxacillin, ampicillin and gentamicin against MRSA strains by the broth microdilution method. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time-kill assay. The membrane-permeabilizing agents and ATP synthase inhibitors were employed to explore their impact on the antibacterial ability of DMC. Western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. Results The MIC of DMC against MRSA is 62.5 µg/ml by broth microdilution method. The synergy between DMC and gentamicin was confirmed by checkerboard method and time-kill assay. When ATP synthase inhibitors blocked the metabolic ability of bacteria, the antibacterial effect of DMC was enhanced. The production of penicillin-binding protein 2a (PBP2a) protein and related genes were reduced by DMC at sub-inhibitory concentrations. In addition, DMC hindered the translation of staphylococcal enterotoxin and the transcription of related gene. Conclusions Based on our results, DMC has a significant inhibitory effect on the vitality of MRSA, and it can be inferred that the mechanism by which DMC reverses MRSA resistance is related to the ability of DMC to block resistance determinants (PBP2a and β-lactamase) and S. aureus exotoxin. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.