Confronted with the severe situation that the pace of resistance acquisition is faster than the clinical introduction of new
antibiotics, health organizations are calling for effective approaches to combat methicillin-resistant Staphylococcus aureus (MRSA)
infections. Here, an approach to treat MRSA through photolysis of
staphyloxanthin, an
antioxidant residing in the microdomain of S. aureus membrane, is reported. This photochemistry process is uncovered through transient absorption imaging and quantitated by absorption spectroscopy, Raman spectroscopy, and mass spectrometry. Photolysis of
staphyloxanthin transiently elevates the membrane permeability and renders MRSA highly susceptible to
hydrogen peroxide attack. Consequently,
staphyloxanthin photolysis by low-level 460 nm light eradicates MRSA synergistically with
hydrogen peroxide and other
reactive oxygen species. The effectiveness of this synergistic
therapy is well validated in MRSA planktonic culture, MRSA-infected macrophage cells, stationary-phase MRSA, persisters, S. aureus biofilms, and two mice
wound infection models. Collectively, the work demonstrates that
staphyloxanthin photolysis is a new therapeutic platform to treat MRSA
infections.