Effect of Tetrandrine against <i>Candida albicans</i> Biofilms

<div><p><i>Candida albicans</i> 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 <i>C. albicans</i>. 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 <i>ECE1</i>, <i>ALS3</i> and <i>HWP1</i>, and abrogated the induction of <i>EFG1</i> and <i>RAS1</i>, 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. <i>In vivo</i>, at a range of concentrations from 4 mg/L to 32 mg/L, TET prolonged the survival of <i>C. albicans-</i>infected <i>Caenorhabditis elegans</i> significantly. This study provides useful information for the development of new strategies to reduce the incidence of <i>C. albicans</i> biofilm-associated infections.</p>