Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening in Saccharomyces cerevisiae
| العنوان: | Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening in Saccharomyces cerevisiae |
|---|---|
| المؤلفون: | Josphat C. Matasyoh, Johannes L. Vrijdag, Joris Winderickx, Geert Callewaert, Elja Eskes, Patrick Van Dijck, Liesbeth Demuyser, Petra D'hooge, Walter Luyten, Purity N. Kipanga |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 5756, p 5756 (2021) Volume 22 Issue 11 |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Antifungal Agents, Mutant, V-ATPase, chemistry.chemical_compound, 0302 clinical medicine, Ca2+ signaling and Ca2+ homeostasis, Homeostasis, Biology (General), Spectroscopy, biology, General Medicine, Hydrogen-Ion Concentration, Computer Science Applications, Cell biology, Mitochondria, Nucleosomes, Chemistry, Vacuolar acidification, TORC1 signaling, Nucleosome mobilization, Sesquiterpenes, Signal Transduction, Vacuolar Proton-Translocating ATPases, Saccharomyces cerevisiae Proteins, QH301-705.5, Saccharomyces cerevisiae, Polygodial, Microbial Sensitivity Tests, Mechanistic Target of Rapamycin Complex 1, Catalysis, Article, Inorganic Chemistry, Mitochondrial Proteins, 03 medical and health sciences, Ribosomal protein, Drug Resistance, Fungal, ubiquitin, Physical and Theoretical Chemistry, Molecular Biology, QD1-999, haploid deletion mutant library, Organic Chemistry, Autophagy, biology.organism_classification, 030104 developmental biology, chemistry, Calcium, vacuolar pH, 030217 neurology & neurosurgery, antifungal |
| الوصف: | 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. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:22 issue:11 ispartof: location:Switzerland status: published |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da98ac47f868b157e818844c0feccb5cTest https://lirias.kuleuven.be/handle/123456789/676156Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....da98ac47f868b157e818844c0feccb5c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |