Overcoming resistance of <i>Candida albicans</i> using photodynamic inactivation

The increasing resistance to conventional antifungal agents, such as Amphotericin B (AmB), has led to a growing demand for alternative therapeutic approaches for Candida albicans, an opportunistic fungal pathogen responsible for infections in immunocompromised patients. This study aimed to evaluate the effectiveness of photodynamic inactivation (PDI) in combination with AmB for controlling C. albicans growth, particularly in its yeast and hyphal forms, and to assess the impact of multiple PDI doses. C. albicans (ATCC 90028) was cultured in yeast and hyphal suspensions that were adjusted to 10⁸ CFU/mL and treated with AmB at varying concentrations (0.065-1.04 μg/mL), with and without PDI. PDI was performed using the photosensitizer curcumin (2.5 μM), activated by a 450 nm LED light source at a fluence of 15 J/cm². The effect of single and repeated PDI doses was evaluated in the fungal biomolecules, which were assessed using Fourier transform infrared (FTIR) spectroscopy. Optical density (OD) measurements quantified fungal growth reduction at 540 nm. The combination of AmB and PDI significantly reduced C. albicans growth, achieving a 75% reduction in the yeast form and an 87.5% reduction in the hyphal form. Two doses of PDI further enhanced antifungal efficacy, particularly against hyphae, which exhibited higher sensitivity to treatment. These findings suggest that PDI enhances the antifungal action of AmB, particularly in more resistant C. albicans forms such as hyphae and biofilms. The observed synergistic effect supports the potential use of PDI as an effective strategy to combat antifungal resistance in clinical applications.