Baicalein suppresses adhesion and biofilm formation in Candida auris

ABSTRACT Candida auris , an emerging multidrug-resistant fungal pathogen, poses a severe global public health threat owing to its high nosocomial transmissibility, considerable mortality, and widespread antifungal resistance. Baicalein (BE), a major bioactive constituent of Scutellaria baicalensis Georgi, exhibits notable antifungal potential, yet its specific molecular mechanisms against C. auris remain poorly elucidated. In this study, we determined the antifungal activity of BE against multiple C. auris isolates, assessed its effects on fungal growth, virulence attributes, adhesion, and biofilm development, validated its in vivo protective efficacy in a Galleria mellonella infection model, and explored the underlying mechanisms via transcriptomic sequencing. BE exerted potent and consistent antifungal activity against all tested strains, with a minimum inhibitory concentration of 1 μg/mL, minimum fungicidal concentrations of 4–8 μg/mL, and a sessile minimum inhibitory concentration of 32 μg/mL. It time- and concentration-dependently suppressed fungal growth, virulence factor expression, adhesion to biological and non-biological surfaces, and biofilm formation, while conferring significant in vivo protection against C. auris infection. Transcriptomic analysis identified 11 adhesion- and biofilm-associated target genes, among which SCF1 and ALS1 served as pivotal regulators. Collectively, BE exerts robust anti -C . auris effects by modulating key target gene expression to interfere with multiple virulence-related processes, providing experimental support for its development as a novel antifungal agent for C. auris infection treatment. IMPORTANCE The emerging multidrug-resistant fungal pathogen Candida auris has become a critical global public health concern. Its pronounced nosocomial transmissibility, high infection-associated mortality, and extensive cross-resistance to mainstream antifungal agents have created substantial unmet needs in clinical treatment and nosocomial infection control. In this study, we systematically validated the in vitro and in vivo antifungal activity of baicalein against C. auris and elucidated the molecular mechanism underlying its modulation of virulence-related genes. Our findings provide a pivotal experimental basis for the development of novel antifungal therapeutics targeting C. auris infections.