Zhao Xiao, Wang Yang, Zhang Qinqin, Huang Yun, Wei Xin, Wu Daming
Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210000, P. R. China.
Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210000, P. R. China.
J Microbiol. 2025 Apr;63(4):e2411008. doi: 10.71150/jm.2411008. Epub 2025 Apr 29.
Candida albicans (C. albicans) is a common opportunistic fungal pathogen that can cause infections ranging from superficial to severe systemic diseases. This study investigates the antifungal effects of metformin on C. albicans and explores its underlying mechanisms. Growth inhibition was assessed via XTT assays, and hyphal formation and morphological changes were observed by light microscope and scanning electron microscopy (SEM). Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were measured with JC-1 and DCFH-DA probes, respectively. Gene expression related to ROS and autophagy was quantified by RT-qPCR, and autophagosomes were visualized using transmission electron microscopy (TEM). Metformin significantly inhibited C. albicans growth and hyphal formation, altered cell morphology, reduced MMP, and increased ROS levels. It activated autophagy in planktonic C. albicans but suppressed it in biofilm forms. Additionally, metformin exhibited synergistic effects with amphotericin B against planktonic C. albicans and with caspofungin against biofilms. The findings suggest that metformin exerts antifungal activity by modulating MMP, ROS levels, and autophagy-related pathways, and enhances the efficacy of specific antifungal drugs.
白色念珠菌是一种常见的机会性真菌病原体，可引起从浅表感染到严重全身性疾病的各种感染。本研究调查了二甲双胍对白色念珠菌的抗真菌作用，并探讨其潜在机制。通过XTT试验评估生长抑制情况，通过光学显微镜和扫描电子显微镜（SEM）观察菌丝形成和形态变化。分别用JC-1和DCFH-DA探针测量线粒体膜电位（MMP）和活性氧（ROS）水平。通过RT-qPCR定量与ROS和自噬相关的基因表达，并使用透射电子显微镜（TEM）观察自噬体。二甲双胍显著抑制白色念珠菌的生长和菌丝形成，改变细胞形态，降低MMP，并增加ROS水平。它激活浮游白色念珠菌中的自噬，但抑制生物膜形式中的自噬。此外，二甲双胍与两性霉素B对浮游白色念珠菌以及与卡泊芬净对生物膜均表现出协同作用。研究结果表明，二甲双胍通过调节MMP、ROS水平和自噬相关途径发挥抗真菌活性，并增强特定抗真菌药物的疗效。
