Effect of Shikonin Against Candida albicans Biofilms

Abstract

Candidiasis is often associated with the formation of biofilms. <i>Candida albicans</i> biofilms are inherently resistant to many clinical antifungal agents and have increasingly been found to be the sources of <i>C. albicans</i> infections. Novel antifungal agents against <i>C. albicans</i> biofilms are urgently needed. The aim of this study was to investigate the effect of shikonin (SK) against <i>C. albicans</i> biofilms and to clarify the underlying mechanisms. XTT reduction assay showed that SK could not only inhibit the formation of biofilms but also destroy the maintenance of mature biofilms. In a mouse vulvovaginal candidiasis (VVC) model, the fungal burden was remarkably reduced upon SK treatment. Further study showed that SK could inhibit hyphae formation and reduce cellular surface hydrophobicity (CSH). Real-time reverse transcription-PCR analysis revealed that several hypha- and adhesion-specific genes were differentially expressed in SK-treated biofilm, including the downregulation of ECE1, HWP1, EFG1, CPH1, RAS1, ALS1, ALS3, CSH1 and upregulation of TUP1, NRG1, BCR1. Moreover, SK induced the production of farnesol, a quorum sensing molecule, and exogenous addition of farnesol enhanced the antibiofilm activity of SK. Taken together, these results indicated that SK could be a favorable antifungal agent in the clinical management of <i>C. albicans</i> biofilms.