Repurposing of quinine as an antifungal antibiotic: Identification of molecular targets in Candida albicans.

Abstract

Quinine, a component of the bark of the cinchona tree, is commonly used to treat malaria. The present study focused on the identification of anti-Candida albicans activity of quinine and its mechanism of action. Quinine showed planktonic growth inhibitory activity at 0.5 mg/mL and fungicidal activity at 4 mg/mL concentration. Time-dependent killing of C. albicans cells was seen after the treatment of quinine at 4 mg/mL concentration. The MIC₅₀ of quinine against yeast to hyphal morphogenesis, adhesion and biofilm formation of C. albicans were observed at 0.25 mg/mL, 1 mg/mL and 0.031 mg/mL, respectively. Scanning electron microscopy analysis of architecture of quinine treated C. albicans biofilm at 2 mg/mL concentration revealed that biofilm formation was significantly inhibited by the treatment of quinine. Quinine also able to inhibit ergosterol synthesis in C. albicans at the concentration range of 2 to 0.062 mg/mL. Quinine could arrest the cell cycle of C. albicans G2/M and S phase at 0.5 mg/mL. qRT-PCR study has demonstrated that the expression of SOD2 and CAT genes in C. albicans was upregulated by 5-fold and 6-fold, respectively in the presence of quinine at 0.5 mg/mL. To check the in vivo antifungal efficacy of quinine, an experiment was carried out in silkworm animal model and it was observed that quinine exhibits antifungal potential against C. albicans pathogenesis. These findings suggest the potential of quinine as a repurposed agent against C. albicans infections.