Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers, like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including protoporphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy’s broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases.

Over the past few decades, phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including porphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy's broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases.

As the leading cause of fungal skin infections around the globe, dermatophytes are responsible for a multitude of skin ailments, ranging from athlete’s foot to ringworm. Due to the combination of its growing prevalence and antifungal misuse, antifungal-resistant dermatophyte strains like Trichophyton indotineae have begun to emerge, posing a significant global health risk. The emergence of these resistant dermatophytes highlights a critical need to identify alternative methods of treating dermatophyte infections. In our study, we utilized a 405 nm LED to establish that blue light can effectively inactivate catalase within a variety of both susceptible and resistant dermatophytes. Through this catalase inactivation process, light-treated dermatophytes were found to exhibit increased sensitivity to reactive oxygen species (ROS)-producing agents, improving the performance of antimicrobial agents such as H₂O₂ and amphotericin B. Our findings further demonstrate that light-induced catalase inactivation can inhibit the formation and polarized growth of hyphae from dermatophytes, suppressing biomass formation. Thus, by increasing ROS sensitization and inhibiting hyphal development, catalase-deactivating blue light offers a potential non-invasive and non-drug-reliant method of managing dermatophyte infections, opening new avenues for the potential treatment of these common infections in conjunction with existing treatments.