Myricetin Exerts Antibiofilm Effects on <i>Candida albicans</i> 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 <i>Candida</i> (<i>C.</i>) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both flu...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/11/5/398 |
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| Summary: | Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating <i>Candida</i> (<i>C.</i>) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical <i>Candida</i> strains, with a particular focus on its inhibitory effects on <i>C. albicans</i> biofilms. Antifungal susceptibility was evaluated on <i>Candida</i> spp. by the broth microdilution method, and the impact of myricetin on <i>C. albicans</i> 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 (<i>ALS3</i>, <i>HWP1</i>, <i>ECE1, UME6</i>, <i>HGC1</i>) and cAMP-dependent protein kinase regulation (<i>RAS1, CYR1, EFG1</i>) 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 <i>Candida</i> biofilms after exposure to MYR and FLC. The in vivo toxicity of myricetin was evaluated by survival analysis using the <i>Galleria mellonella</i> model. Myricetin significantly suppressed key genes related to hyphae development (<i>RAS1</i>, <i>CYR1</i>, <i>EFG1</i>, <i>UME6</i>, and <i>HGC1</i>) and adhesion (<i>ALS3</i> and <i>HWP1</i>) in both clinical and reference <i>Candida</i> strains at a concentration of 640 µg/mL. FESEM analysis revealed that myricetin inhibited hyphae growth and elongation in <i>C. albicans</i>. This study highlights the promising antibiofilm potential of myricetin through a significant inhibition of biofilm formation and hyphal morphogenesis. |
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| ISSN: | 2309-608X |