Aspirin damages the cell wall of Saccharomyces cerevisiae by inhibiting the expression and activity of dolichol-phosphate mannose synthase 1

Aspirin is a commonly used anti-inflammatory, analgesic and antithrombotic drug. It has attracted attention due to its potential antifungal therapeutic effect; however, the molecular mechanism is poorly understood. Here, the effects of aspirin on the cell wall of Saccharomyces cerevisiae were explored. We observed by scanning electron microscopy that aspirin could damage the cell wall ultrastructure. Meanwhile, a cellular surface hydrophobicity (CSH) assay showed that aspirin increased the hydrophobicity of the yeast cell surface. A drug sensitivity assay indicated that the overexpression of dolichol phosphate mannose synthase 1 (DPM1) reversed the cell wall damage and decreased the CSH induced by aspirin. Importantly, aspirin decreased the expression and enzyme activity of DPM1 in S. cerevisiae. Molecular docking results demonstrated that aspirin could directly bind to the Ser141 site of DPM1. Similarly, we found that aspirin damaged the cell wall and inhibited the expression of DPM1 in Candida albicans. These findings improve the current understanding of the action mode of aspirin and provide new strategies for antifungal drug design.