{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:03:06Z","timestamp":1760234586181,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C14\/17\/063"],"award-info":[{"award-number":["C14\/17\/063"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polygodial is a \u201chot\u201d 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms22115756","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T11:33:20Z","timestamp":1622201600000},"page":"5756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening in Saccharomyces cerevisiae"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-1404","authenticated-orcid":false,"given":"Purity N.","family":"Kipanga","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Biology, Animal Physiology and Neurobiology, KU Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liesbeth","family":"Demuyser","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium"},{"name":"VIB-KU Leuven Center for Microbiology, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8085-3390","authenticated-orcid":false,"given":"Johannes","family":"Vrijdag","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Molecular Design and Synthesis, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elja","family":"Eskes","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium"},{"name":"VIB-KU Leuven Center for Microbiology, 3000 Leuven, Belgium"},{"name":"Department of Biology, Functional Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"D\u2019hooge","sequence":"additional","affiliation":[{"name":"The Yeast Hub Lab, KU Leuven, Campus Kulak, 8500 Kortrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josphat","family":"Matasyoh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Egerton University, Njoro 20107, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert","family":"Callewaert","sequence":"additional","affiliation":[{"name":"The Yeast Hub Lab, KU Leuven, Campus Kulak, 8500 Kortrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-7733","authenticated-orcid":false,"given":"Joris","family":"Winderickx","sequence":"additional","affiliation":[{"name":"Department of Biology, Functional Biology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-897X","authenticated-orcid":false,"given":"Patrick","family":"Van Dijck","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium"},{"name":"VIB-KU Leuven Center for Microbiology, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-5816","authenticated-orcid":false,"given":"Walter","family":"Luyten","sequence":"additional","affiliation":[{"name":"Department of Biology, Animal Physiology and Neurobiology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kubo, I., Lee, Y.-W., Pettei, M., Pilkiewicz, F., and Nakanishi, K. 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