Cordycepin is an effective antifungal agent and targets multiple pathways and structures in yeasts

Abstract Aim Several kinds of harmful yeasts may cause spoilage of foods and even endanger health. As a natural active ingredient, cordycepin has been found to be effective against bacteria. However, the antifungal mechanism of the cordycepin is uncertain. In this work, the antifungal activity and mechanism of cordycepin against yeasts has been studied. Methods and Results The effects of cordycepin on cell structure, biomacromolecule substances, respiratory metabolism, and nucleic acid were analyzed through scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrophotometer, fluorescence titration, etc. The results indicated that cordycepin was more effective in antifungal activity against Saccharomyces cerevisiae, Candida albicans and Zygosaccharomyces rouxii, compared to potassium sorbate. SEM observations revealed irreversible damage to the cell wall and membrane, leading to intracellular biological macromolecules leakage, which was proved by the quantification of biological macromolecular substances. Moreover, it was found that cordycepin inhibited respiratory metabolic pathways of S. cerevisiae, C. albicans and Z. rouxii by affecting the HMP and TCA pathways. In addition, cordycepin had intercalated binding and electrostatic interaction with DNA. Conclusions Cordycepin exhibited high antifungal activity with a minimum inhibitory concentration of 0.125–0.05 mg/ml against Saccharomyces cerevisiae, Candida albicans and Zygosaccharomyces rouxii. Cordycepin exerted antibacterial effects through damaging cell membranes, inhibiting respiratory metabolism and binding DNA to affect fungal physiological functions.