Harmine-Antiseptic Dual Combination Photodynamic Therapy for Targeting Methicillin-Resistant Staphylococcus aureus

Chronic wound infections, particularly those caused by antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), pose a persistent clinical challenge, espe-cially in light of escalating antibiotic resistance. Alternative strategies such as antibacterial photodynamic therapy (aPDT) have emerged due to their localized, resistance-independent mechanisms of action[1]. In aPDT, bacterial cells are damaged by photosensitizers (PS) that are activated by light-induced reactions[2]. Harmine (HA), is a natural PS, present in plants and animals, reported for photodynamic cancer treatment[3]. This work explored HA photody-namic activity and its combination with marketed antiseptics, namely octenidine dihydrochlo-ride (OCT), polyhexamethylene biguanide (PHMB), and hydrogen peroxide against S. aureus clinical strain (MJMC568-B: MRSA). The antibacterial effects of individual agents were as-sessed by broth microdilution assay, while the combinatory effects were evaluated through checkerboard and disk diffusion assays, for determination of minimum inhibitory concentra-tion (MIC), minimum bactericidal concentration (MBC) and inhibition diameter zones (IZD). Photodynamic potential of HA was both accessed independently and in combination by irra-diating with a UV light-emitting diode (LED) system at 365 nm and quantifying through colony-forming unit (CFU) analysis. The results revealed that HA-antiseptics combinations showed synergic behavior. Photodynamic treatment with UV-A light enhanced antibacterial capacity of HA, significantly reducing S. aureus culturability and achieving total inactivation (7.98 ± 0.03 log reduction (CFU/mL)). These results highlight the potential of HA-antiseptics dual-combina-tions for photodynamic treatment of chronic wounds.