Vitamin K3 (Menadione) is a multifunctional microbicide acting as a photosensitizer and synergizing with blue light to kill drug-resistant bacteria in biofilms

Cutaneous bacterial wound infections typically involve gram-positive cocci such as Staphylococcus aureus (SA) and usually become biofilm infections. Bacteria in biofilms may be 100–1000-fold more resistant to an antibiotic than the clinical laboratory minimal inhibitory concentration (MIC) for that antibiotic, contributing to antimicrobial resistance (AMR). AMR is a growing global threat to humanity. One pathogen–antibiotic resistant combination, methicillin–resistant SA (MRSA) caused more deaths globally than any other such combination in a recent worldwide statistical review. Many wound infections are accessible to light. Antimicrobial phototherapy, and particularly antimicrobial blue light therapy (aBL) is an innovative non-antibiotic approach often overlooked as a possible alternative or adjunctive therapy to reduce antibiotic use. We therefore focused on aBL treatment of biofilm infections, especially MRSA, focusing on in vitro and ex vivo porcine skin models of bacterial biofilm infections. Since aBL is microbicidal through the generation of reactive oxygen species (ROS), we hypothesized that menadione (Vitamin K3), a multifunctional ROS generator, might enhance aBL. Our studies suggest that menadione can synergize with aBL to increase both ROS and microbicidal effects, acting as a photosensitizer as well as an ROS recycler in the treatment of biofilm infections. Vitamin K3/menadione has been given orally and intravenously worldwide to thousands of patients. We conclude that menadione/Vitamin K3 can be used as an adjunct to antimicrobial blue light therapy, increasing the effectiveness of this modality in the treatment of biofilm infections, thereby presenting a potential alternative to antibiotic therapy, to which biofilm infections are so resistant. Vitamin K3 (Menadione) potentiates the effect of antimicrobial bluelight to increase both ROS and oxidative stress to kill drug-resistant bacteria in biofilms in the wounds. [Display omitted] •Menadione increased antimicrobial effects of blue light (aBL, 405 nm) against MDR pathogenic bacteria by 100-1,000 fold.•ROS produced by menadione plus aBL increases intracellular oxidative stress, with more MDR bacterial killing in biofilms.•Menadione increased production of ROS by 405 nm irradiation, acting as a photosensitizer.