Annihilation of Methicillin-resistant Staphylococcus aureus via Photobleaching of Staphyloxanthin

Abstract

Given that the dearth of new antibiotic development loads an existential burden on successful infectious disease therapy1, health organizations are calling for alternative approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report a drug-free photonic approach to eliminate MRSA through photobleaching of staphyloxanthin, an indispensable membrane-bound antioxidant of S. aureus2-5. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by absorption spectroscopy and mass spectrometry, decomposes staphyloxanthin and sensitizes MRSA to reactive oxygen species attack. Consequently, staphyloxanthin bleaching by low-level blue light eradicates MRSA synergistically with external or internal reactive oxygen species. The effectiveness of this synergistic therapy is validated in MRSA culture, MRSA-infected macrophage cells, S. aureus biofilms, and a mouse wound infection model. Collectively, these findings highlight broad applications of staphyloxanthin photobleaching for treatment of MRSA infections.