title: Effect of tetrandrine against Candida albicans biofilms.
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.
authors.affiliation: New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China ; Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lan-Xue
authors.initials: LX
authors.lastname: Zhao
authors.forename: De-Dong
authors.initials: DD
authors.lastname: Li
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Hu
authors.forename: Gan-Hai
authors.initials: GH
authors.lastname: Hu
authors.forename: Lan
authors.initials: L
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D005656:Fungal Proteins; C009438:tetrandrine