Methicillin-resistant Staphylococcus aureus (MRSA) possesses array of strategies to evade antibiotics through mutational inactivation, hiding inside host immune cells or concealing inside the biofilm in a sessile form. We report a drug-free approach to eradicate MRSA through blue-light bleaching of staphyloxanthin (STX), an anti-oxidative carotenoid residing inside the cell membrane of S. aureus. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by mass spectrometry, decomposes STX and sensitizes MRSA to reactive oxygen species attack. Consequently, photobleaching using low-level blue light exhibits high-level synergy when combined with low-concentration of hydrogen peroxide. Antimicrobial effectiveness of this synergistic therapy is validated in MRSA culture, MRSA-infected macrophage cells, biofilm, and a mouse wound infection model. Collectively, these findings highlight broad applications of STX photobleaching for MRSA-infected diseases.
