Myricetin Exerts Antibiofilm Effects on by Targeting the RAS1/cAMP/EFG1 Pathway and Disruption of the Hyphal Network.

Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating () infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical strains, with a particular focus on its inhibitory effects on biofilms. Antifungal susceptibility was evaluated on spp. by the broth microdilution method, and the impact of myricetin on biofilms was determined using the Cell Counting Kit-8 (CCK-8) assay. To understand the molecular mechanisms underlying the antibiofilm properties of myricetin, expression analysis of genes in the RAS1/cAMP/EFG1 pathway (, , , ) and cAMP-dependent protein kinase regulation () involved in the transition from yeast to hyphae was performed. Field emission scanning electron microscopy (FESEM) was used to study the ultrastructural changes and morphological dynamics of biofilms after exposure to MYR and FLC. The in vivo toxicity of myricetin was evaluated by survival analysis using the model. Myricetin significantly suppressed key genes related to hyphae development (, , , , and ) and adhesion ( and ) in both clinical and reference strains at a concentration of 640 µg/mL. FESEM analysis revealed that myricetin inhibited hyphae growth and elongation in . This study highlights the promising antibiofilm potential of myricetin through a significant inhibition of biofilm formation and hyphal morphogenesis.