LAUSR

The emergence of multidrug-resistant bacteria has become a real threat and we are fast running out of treatment options. A combinatory strategy is explored here to eradicate multidrug-resistant Staphlococcus aureus and Pseudomonas aeruginosa including planktonic cells, established biofilms, and persisters as high as 7.5 log bacteria in less than 30 min. Blue-laser and thymol together rapidly sterilized acute infected or biofilm-associated wounds and successfully prevented systematic dissemination in mice. Mechanistically, blue-laser and thymol instigated oxidative bursts exclusively in bacteria owing to abundant proporphyrin-like compounds produced in bacteria over mammalian cells, which transformed harmless thymol into blue-laser sensitizers, thymoquinone and thymohydroquinone. Photo-excitations of thymoquinone and thymohydroquinone augmented reactive oxygen species production and initiated a torrent of cytotoxic events in bacteria while completely sparing the host tissue. The investigation unravels a previously unappreciated property of thymol as a pro-photosensitizer analogous to a prodrug that is activated only in bacteria. Multidrug-resistant bacteria are a real threat to human health. Here, the authors investigate a combinatory strategy using blue-laser and thymol against Staphylococcus aureus and Pseudomonas aeruginosa . Blue-laser and thymol succesfully sterilized acute infected or biofilm-associated wounds and prevented systematic dissemination in mice. Compared with mammalian cells, bacteria contain abundant proporphyrin-like compounds that transform harmless thymol into blue-laser sensitizers, thymoquinone and thymohydroquinone. Photo-excitation of thymoquinone and thymohydroquinone augmented reactive oxygen species production in bacteria while completely sparing the host tissue.