Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening in Saccharomyces cerevisiae

Abstract

Polygodial is a “hot” peppery-tasting sesquiterpenoid that was first described for its anti-feedant activity against African armyworms. Using the haploid deletion mutant library of Saccharomyces cerevisiae, a genome-wide mutant screen was performed to shed more light on polygodial’s antifungal mechanism of action. We identified 66 deletion strains that were hypersensitive and 47 that were highly resistant to polygodial treatment. Among the hypersensitive strains, an enrichment was found for genes required for vacuolar acidification, amino acid biosynthesis, nucleosome mobilization, the transcription mediator complex, autophagy and vesicular trafficking, while the resistant strains were enriched for genes encoding cytoskeleton-binding proteins, ribosomal proteins, mitochondrial matrix proteins, components of the heme activator protein (HAP) complex, and known regulators of the target of rapamycin complex 1 (TORC1) signaling. WE confirm that polygodial triggers a dose-dependent vacuolar alkalinization and that it increases Ca2+ influx and inhibits glucose-induced Ca2+ signaling. Moreover, we provide evidence suggesting that TORC1 signaling and its protective agent ubiquitin play a central role in polygodial resistance, suggesting that they can be targeted by polygodial either directly or via altered Ca2+ homeostasis.

Thymus richardii subsp. nitidus (Guss.) Jalas Essential Oil: An Ally against Oral Pathogens and Mouth Health

“…Although these authors also showed that this class of compounds inhibited both respiration and the synthesis of cellular macromolecules, such as DNA, RNA, proteins, and polysaccharides, they concluded that these were secondary effects of the cell damage caused by polygodial since the inhibition of these macromolecules was not specific [78]. Probably, the simultaneous action of all the compounds contained in the EO is essential to exerting the antimicrobial activity.…”