Fewer antibiotics are available for effective management of bacterial infections to date owing to increasing multiple-drug resistance (MDR). Here, we expand our early success in combination of 405 nm blue light irradiation with phenolic compounds to sufficiently kill blue light-refractory MDR Escherichia coli (E. coli). p-Toluquinone (p-TQ) alongside blue light inactivated 7.3 logE. coli within 6 min, whereas either alone was totally ineffective. A similar killing efficacy was attained with four other pathogens commonly seen in hospital-acquired infections and Enterococcus faecalis (Ef) that don’t produce porphyrins-like molecules. The combinatory therapy prevented recurrence of E. coli infection in skin scratch wounds of murine. The bactericidal activity was ascribed to reactive oxygen species (ROS) generation triggered by blue light-mediated excitation of p-TQ, which is less likely to induce resistance because of multi-targeted and non-specific nature of ROS. Remarkably, toxic p-TQ became harmless to mammalian cells after brief exposure to blue light while retaining its bactericidal activity. The opposite effect of blue light on p-TQ activity unravels a novel, simple strategy to detoxify p-TQ and its combination with blue light as a safe and efficacious bactericidal modality for managing MDR bacterial infections.
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