Vitamin K3 (menadione) acts as a photosensitizer with antimicrobial blue light (aBL) to kill drug-resistant bacteria in biofilms, including a porcine skin explant wound model — MHSRS 2023

Negri LB, Fairnelli WA, Korupolu S, Tam J, Gelfand J

Abstract accepted for a poster session at the 2023 Military Health System Research Symposium

Bacterial biofilm infections play a critical role in wound pathogenesis, enabling bacteria to defend themselves against both antibiotics and host defenses. They enhance persistence of infection, permitting spread of infection, delay of healing, and the development of antimicrobial resistance, all potentially contributing to sepsis and death from wounds. Antibiotic drugs are 10- to- 1,000-fold less effective against bacterial biofilm cultures than standard mean inhibitory concentration (MIC) reports indicate. We are developing ways to bring antimicrobial blue light (aBL) into patient care, specifically for treating wounds, with a special focus on the potential for this mode of therapy to overcome antimicrobial resistance (AMR) in biofilms. Antimicrobial blue light (herein 405nm) involves photochemical reactions with endogenous chromophores in bacteria that result in the release of reactive oxygen species (ROS), which are highly cytotoxic for bacteria. However, aBL penetrates tissue poorly, so this modality is best suited to the treatment of visible, light- accessible wounds. In this setting, aBL is a topical treatment to substantially reduce the bacterial bioburden, preventing more serious, penetrating infection. Thus, topically acting agents enhancing aBL would be useful. We have previously demonstrated that vitamin K 3/menadione could enhance aBL antimicrobial activity. A photosensitizer is a molecule that absorbs light and undergoes a photochemical reaction in which it typically donates an electron to a target substrate, generating reactive molecular species which, in turn, may have a biological effect. In this report, we have demonstrated that menadione acts as a therapeutic photosensitizer to kill bacteria upon illumination with aBL, elucidating some of the mechanisms, and additionally demonstrating this adjuvant effect in a porcine skin explant, ex vivo wound- biofilm model.