Meral Ocal Melda, Aydin Merve, Sumlu Esra, Korucu Emine Nedime, Ozturk Ali
Department of Biotechnology, Faculty of Science, Mersin University, Mersin 33343, Turkey.
Department of Medical Microbiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, Turkey.
J Fungi (Basel). 2025 May 21;11(5):398. doi: 10.3390/jof11050398.
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.
现有药物抗真菌耐药性的增加及其副作用促使人们寻找治疗（）感染的替代方法。本研究旨在全面评估天然黄酮杨梅素（MYR）对氟康唑（FLC）耐药和敏感临床菌株的抗真菌疗效，特别关注其对生物膜的抑制作用。采用肉汤微量稀释法评估了杨梅素对（）菌株的抗真菌敏感性，并使用细胞计数试剂盒-8（CCK-8）测定法确定了杨梅素对生物膜的影响。为了解杨梅素抗生物膜特性的分子机制，对参与酵母向菌丝转变的RAS1/cAMP/EFG1途径（，，，）和cAMP依赖性蛋白激酶调节（）中的基因进行了表达分析。使用场发射扫描电子显微镜（FESEM）研究了暴露于MYR和FLC后（）生物膜的超微结构变化和形态动力学。通过使用（）模型进行生存分析评估了杨梅素的体内毒性。在浓度为640 µg/mL时，杨梅素显著抑制了临床和参考（）菌株中与菌丝发育（，，，，和）和粘附（和）相关的关键基因。FESEM分析表明，杨梅素抑制了（）中菌丝的生长和伸长。本研究通过显著抑制生物膜形成和菌丝形态发生，突出了杨梅素具有良好的抗生物膜潜力。
