The Impact of Methylene Blue in Antimicrobial Photodynamic Therapy Against Different Candida Species and Its Synergy with Fluconazole

Abstract

Antifungal resistance in Candida strains has recently increased, especially in C. non-albicans strains, making the development of alternative treatments for fungal infections critical. Antimicrobial photodynamic therapy (aPDT) is a promising alternative treatment that has been successfully used against various infections and microorganisms, including Candida albicans. However, there are still limited studies on C. non-albicans strains, such as Candida tropicalis and Candida glabrata. In this work, the effect of aPDT was evaluated in 18 strains of 3 Candida species: (C. albicans, C. tropicalis and C. glabrata). Synergistic treatments with fluconazole and aPDT using methylene blue (MB) as photosensitizer (PS) were also performed on a C. albicans and a C. tropicalis strain. Resistance to azoles was assessed by Kirby and Bauer disk diffusion method and intracellular MB uptake by cell lysis and spectroscopic analysis. Our results showed that aPDT using MB as PS effectively inhibited the growth of all tested yeast strains in vitro. Even fluconazole-resistant, less-studied strains, such as C. glabrata or C. tropicalis showed significant inhibition, regardless of differences in drug resistance, strain origin, or the MB intracellular concentration. We also observed synergistic effects of aPDT with fluconazole, the combination of sublethal doses of aPDT and fluconazole can effectively eliminate fluconazole-resistant (C. tropicalis) or sensitive (C. albicans) strains. This suggests that aPDT, alone or in combination with antifungal drugs, is a viable alternative treatment for many Candida species