Dioscorea tokoro Makino extract suppresses the growth of Saccharomyces cerevisiae INVSc1 by disrupting the endolysosomal pathway.

Exploring novel antifungal mechanisms is needed because of the side effects of existing treatments and the increasing prevalence of drug resistance. We recently reported that inhibition of the endocytic pathway via a lysosome inhibitor or Fab1/Vac14 suppression enhances the localization of emerald green fluorescent protein-bound β-1,3-glucanase (BGL2-EmGFP) at the tip in Saccharomyces cerevisiae INVSc1, used as a non-pathogenic model. Overexpression of wild-type BGL2-EmGFP, but not an inactive mutant, completely abolished cell proliferation, suggesting that impairing tip growth through dysregulated glucanase activity represents a novel antifungal mechanism. In this study, using a phenotypic screening strategy combining fluorescein isothiocyanate (FITC)-dextran endocytosis/exocytosis assays with BGL2-EmGFP localization analysis, Dioscorea tokoro Makino extract was found to induce dysregulation of the endocytic pathway and promote BGL2-EmGFP localization at the tip, accompanied by growth inhibition in S. cerevisiae INVSc1. These findings suggest that this phenotypic screening strategy provides a promising approach based on a novel antifungal mechanism involving endocytic dysregulation and enhanced BGL2 localization at the tip.