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Abstract
Climate and environmental changes have modified the habitats of fungal pathogens, inflicting devastating effects on livestock and crop production. Additionally, drug-resistant fungi are increasing worldwide, driving the urgent need to identify new molecular scaffolds for development of antifungal agents for humans, animals, and plants. Poacic acid (PA), a plant-derived stilbenoid, was recently discovered to be a novel molecular scaffold that inhibits the growth of several fungi. Its antifungal activity has been associated with perturbation of the production/assembly of fungal cell wall β-1,3-glucan, but its mode of action is not resolved. In this study, we investigated the antifungal activity of PA and its derivatives on a panel of yeast. PA had a fungistatic effect on S. cerevisiae and a fungicidal effect on plasma membrane-damaged Candida albicans mutants. Live cell fluorescent microscopy experiments revealed that PA increases chitin production and modifies its cell wall distribution. Chitin production and cell growth returned to normal after prolonged incubation. The antifungal activity of PA was reduced in the presence of exogenous chitin, suggesting that potentiation of chitin production is a stress response that helps the yeast cell overcome the effect of this antifungal stilbenoid. Growth inhibition was also reduced by metal ions, indicating that PA affects metal homeostasis. These findings suggest that PA has a complex antifungal mechanism of action that involves perturbation of cell wall β-1,3-glucan production/assembly, chitin production, and metal homeostasis.
Supplementary materials
Title
Supporting Information
Description
Yeast strains (Table S1); growth curves (Figure S1-S3); live cell imaging data (Figure S4); disc diffusion assay (Figure S5), detailed synthetic schemes (Scheme S1-S2); MIC values (Table S2); analytic HPLC chromatograms (Figure S6-S15); 1H and 13C NMR spectra (Figures S16-S33).
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