Poacic acid, a ??1,3?glucan–binding antifungal agent, inhibits cell?wall remodeling and activates transcriptional responses regulated by the cell?wall integrity and high?osmolarity glycerol pathways in yeast

As a result of the relatively few available antifungals and increasing frequency resistance to them, development novel is increasingly important. The plant natural product poacic acid (PA) inhibits ?-1,3-glucan synthesis in Saccharomyces cerevisiae has antifungal activity against wide range pathogens. However, mode action PA unclear. Here, we reveal that specifically binds ?-1,3-glucan, its affinity for which ~30-fold chitin. Besides effect on synthase activity, inhibited yeast glucan-elongating Gas1 Gas2 chitin–glucan transglycosylase Crh1. Regarding cellular response PA, transcriptional co-regulation was mediated by parallel activation cell-wall integrity (CWI) high-osmolarity glycerol signaling pathways. Despite targeting remodeling, profiles regulatory circuits activated caspofungin, zymolyase, differed, indicating their effects CWI have different mechanisms. growth strains indicated it distinct from echinocandins, suggesting unique agent.