Blue Dye and Red Light, a Dynamic Combination for Prophylaxis and Treatment of Cutaneous Candida albicans Infections in Mice

Abstract

ABSTRACTThe objective of this study was to investigate photodynamic therapy (PDT), using blue dye and red light, for prophylaxis and treatment of cutaneousCandida albicansinfections in mice. A mouse model of skin abrasion infected withC. albicanswas developed by inoculating wounds measuring 1.2 cm by 1.2 cm with 106or 107CFU. The use of a luciferase-expressing strain ofC. albicansallowed real-time monitoring of the extent of infection in mice noninvasively through bioluminescence imaging. The phenothiazinium salts toluidine blue O (TBO), methylene blue (MB), and new methylene blue (NMB) were compared as photosensitizers (PS) for the photodynamic inactivation ofC. albicansin vitro. PDTin vivowas initiated either at 30 min or at 24 h after fungal inoculation to investigate the efficacies of PDT for both prophylaxis and treatment of infections. Light at 635 ± 15 nm or 660 ± 15 nm was delivered with a light dose of 78 J/cm2(for PDT at 30 min postinfection) or 120 J/cm2(for PDT at 24 h postinfection) in multiple exposures with bioluminescence imaging taking place after each exposure of light.In vitrostudies showed that NMB was superior to TBO and MB as the PS in the photodynamic inactivation ofC. albicans. The efficacy of PDT was related to the ratio of PS concentration to fungal cell density. PDTin vivoinitiated either at 30 min or at 24 h postinfection significantly reducedC. albicansburden in the infected mouse skin abrasion wounds. These data suggest that PDT is a viable approach for prophylaxis and treatment of cutaneousC. albicansinfections.