Effect of Tetrandrine against Candida albicans Biofilms |
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| Authors: | Lan-Xue Zhao De-Dong Li Dan-Dan Hu Gan-Hai Hu Lan Yan Yan Wang Yuan-Ying Jiang |
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| Affiliation: | 1. New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China.; 2. Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.; 3. Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.; Ghent University, Belgium, |
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| Abstract: | Candida albicans is the most common human fungal pathogen and has a high propensity to develop biofilms that are resistant to traditional antifungal agents. In this study, we investigated the effect of tetrandrine (TET) on growth, biofilm formation and yeast-to-hypha transition of C. albicans. We characterized the inhibitory effect of TET on hyphal growth and addressed its possible mechanism of action. Treatment of TET at a low concentration without affecting fungal growth inhibited hyphal growth in both liquid and solid Spider media. Real-time RT-PCR revealed that TET down-regulated the expression of hypha-specific genes ECE1, ALS3 and HWP1, and abrogated the induction of EFG1 and RAS1, regulators of hyphal growth. Addition of cAMP restored the normal phenotype of the SC5314 strain. These results indicate that TET may inhibit hyphal growth through the Ras1p-cAMP-PKA pathway. In vivo, at a range of concentrations from 4 mg/L to 32 mg/L, TET prolonged the survival of C. albicans-infected Caenorhabditis elegans significantly. This study provides useful information for the development of new strategies to reduce the incidence of C. albicans biofilm-associated infections. |
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