Antifungal and Antibiofilm Activities of Flavonoids Against : Focus on 3,2'-dihydroxyflavone As a Potential Therapeutic Agent

Effective management of microbial biofilms holds significance within food and medical environments. , 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 . 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 (, , and ) but upregulated the biofilm/hyphal regulators (, , , and ). 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 .