Antifungal and antibiofilm activities of flavonoids against Candida albicans: Focus on 3,2′-dihydroxyflavone as a potential therapeutic agent

Abstract

Effective management of microbial biofilms holds significance within food and medical environments. Candida albicans, an opportunistic fungus, forms mucosal biofilms closely linked to candidiasis and drug-resistant infections due to their drug tolerance. Morphologic change from yeast to filamentous cells is a key virulence factor and a prerequisite for biofilm development. This study investigated the anti-fungal and antibiofilm activities of 20 flavonoids against C. albicans. With their known antioxidant capabilities, flavonoids hold promise in combating infections associated with biofilms. Among them, flavone and its derivatives exhibited moderate antifungal activity, 3,2′-dihydroxyflavone (3,2′-DHF) at 1 μg/mL exhibited strong antibiofilm activity (MIC 50 μg/mL). In addition, 3,2′-DHF dramatically inhibited cell aggregation and germ tube/hyphae formation. Transcriptomic analyses revealed that flavone and 3,2′-DHF behaved differently, as 3,2′-DHF downregulated the expressions of germ tube/hyphae-forming and biofilm-related genes (ECE1, HWP1, TEC1, and UME6) but upregulated the biofilm/hyphal regulators (CHK1, IFD6, UCF1, and YWP1). Tests evaluating toxicity with plant and nematode models revealed that flavone and 3,2′-DHF exhibited mild toxicity. Current results indicate that hydroxylated flavone derivatives can enhance anti-fungal and antibiofilm activities and provide a source of potential anti-fungal agents against drug-resistant C. albicans.