[P3-2-37] Effects of hinokitiol, lactoferrin, and cystatin on combating fluconazole drug resistance in Candida albicans
Keywords:ヒノキチオール、薬剤耐性、Candida albicans
Introduction
In recent years, attention has been focused on the problem of drug resistance. As there are relatively low numbers and types of antifungal drugs, drug selection becomes a major issue when resistance develops. Therefore, this study aims to identify a drug that relieves fluconazole (FLCZ) drug resistance with a drug that differs from existing antifungal drugs.
Materials & Methods
The antifungal action of hinokitiol, lactoferrin, and cystatin on Candida albicans strain 40009 was examined via the microdilution method, with the FLCZ resistance–releasing action also being examined. AD-Cdr1 (resistant strain), generated by integrating C. albicans Cdr1 into baker's yeast AD (parent strain) that lacks seven transporter genes related to drug efflux and is highly expressed, was used. In addition, the antifungal effect of hinokitiol on C. albicans germ tube formation was investigated over time.
Results
In the broth microdilution method, hinokitiol, lactoferrin, and cystatin inhibited the growth of C. albicans when administered alone. When hinokitiol and lactoferrin were used in combination with FLCZ, the C. albicans growth inhibition curve shifted to the low FLCZ concentration side in resistant strains. C. albicans to which 3 μg/mL hinokitiol was added did not form germ tubes, even after 24 h.
Discussion
In the microdilution method, hinokitiol, lactoferrin, and cystatin exhibited antifungal effects when administered alone. Hinokitiol at 2 μg/mL and lactoferrin at 100 μg/mL exhibited a drug resistance–releasing effect when used in combination with FLCZ. Hinokitiol at 3 μg/mL inhibited germ tube formation even after 24 h, suggesting that it inhibits the conversion of C. albicans from yeast cells to mycelial cells.
In recent years, attention has been focused on the problem of drug resistance. As there are relatively low numbers and types of antifungal drugs, drug selection becomes a major issue when resistance develops. Therefore, this study aims to identify a drug that relieves fluconazole (FLCZ) drug resistance with a drug that differs from existing antifungal drugs.
Materials & Methods
The antifungal action of hinokitiol, lactoferrin, and cystatin on Candida albicans strain 40009 was examined via the microdilution method, with the FLCZ resistance–releasing action also being examined. AD-Cdr1 (resistant strain), generated by integrating C. albicans Cdr1 into baker's yeast AD (parent strain) that lacks seven transporter genes related to drug efflux and is highly expressed, was used. In addition, the antifungal effect of hinokitiol on C. albicans germ tube formation was investigated over time.
Results
In the broth microdilution method, hinokitiol, lactoferrin, and cystatin inhibited the growth of C. albicans when administered alone. When hinokitiol and lactoferrin were used in combination with FLCZ, the C. albicans growth inhibition curve shifted to the low FLCZ concentration side in resistant strains. C. albicans to which 3 μg/mL hinokitiol was added did not form germ tubes, even after 24 h.
Discussion
In the microdilution method, hinokitiol, lactoferrin, and cystatin exhibited antifungal effects when administered alone. Hinokitiol at 2 μg/mL and lactoferrin at 100 μg/mL exhibited a drug resistance–releasing effect when used in combination with FLCZ. Hinokitiol at 3 μg/mL inhibited germ tube formation even after 24 h, suggesting that it inhibits the conversion of C. albicans from yeast cells to mycelial cells.