Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis

Abstract Repetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylari...

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Autores principales:	Kwanrutai Watchaputi, Pichayada Somboon, Nipatthra Phromma-in, Khanok Ratanakhanokchai, Nitnipa Soontorngun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86fbe62d577140e7a6648753ec1e801a
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spelling	oai:doaj.org-article:86fbe62d577140e7a6648753ec1e801a2021-12-02T18:15:33ZActin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis10.1038/s41598-021-87342-42045-2322https://doaj.org/article/86fbe62d577140e7a6648753ec1e801a2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87342-4https://doaj.org/toc/2045-2322Abstract Repetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylaria sp. BCC 1067 of tropical forests. In a model yeast Saccharomyces cerevisiae, ECQ is more toxic in the erg6∆ strain, which has previously been shown to allow higher uptake of many hydrophilic toxins. We selected one pathway to study the effects of ECQ at very high levels on transcription: the ergosterol biosynthesis pathway, which is unlikely to be the primary target of ECQ. Ergosterol serves many functions that cholesterol does in human cells. ECQ’s transcriptional effects were correlated with altered sterol and triacylglycerol levels. In the ECQ-treated Δerg6 strain, which presumably takes up far more ECQ than the wild-type strain, there was cell rupture. Increased actin aggregation and lipid droplets assembly were also found in the erg6∆ mutant. Thereby, ECQ is suggested to sensitize yeast cells lacking ERG6 through actin-targeting and consequently but not primarily led to disruption of lipid homeostasis. Investigation of cytochalasins may provide valuable insight with potential biopharmaceutical applications in treatments of fungal infection, cancer or metabolic disorder.Kwanrutai WatchaputiPichayada SomboonNipatthra Phromma-inKhanok RatanakhanokchaiNitnipa SoontorngunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kwanrutai Watchaputi Pichayada Somboon Nipatthra Phromma-in Khanok Ratanakhanokchai Nitnipa Soontorngun Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
description	Abstract Repetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylaria sp. BCC 1067 of tropical forests. In a model yeast Saccharomyces cerevisiae, ECQ is more toxic in the erg6∆ strain, which has previously been shown to allow higher uptake of many hydrophilic toxins. We selected one pathway to study the effects of ECQ at very high levels on transcription: the ergosterol biosynthesis pathway, which is unlikely to be the primary target of ECQ. Ergosterol serves many functions that cholesterol does in human cells. ECQ’s transcriptional effects were correlated with altered sterol and triacylglycerol levels. In the ECQ-treated Δerg6 strain, which presumably takes up far more ECQ than the wild-type strain, there was cell rupture. Increased actin aggregation and lipid droplets assembly were also found in the erg6∆ mutant. Thereby, ECQ is suggested to sensitize yeast cells lacking ERG6 through actin-targeting and consequently but not primarily led to disruption of lipid homeostasis. Investigation of cytochalasins may provide valuable insight with potential biopharmaceutical applications in treatments of fungal infection, cancer or metabolic disorder.
format	article
author	Kwanrutai Watchaputi Pichayada Somboon Nipatthra Phromma-in Khanok Ratanakhanokchai Nitnipa Soontorngun
author_facet	Kwanrutai Watchaputi Pichayada Somboon Nipatthra Phromma-in Khanok Ratanakhanokchai Nitnipa Soontorngun
author_sort	Kwanrutai Watchaputi
title	Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
title_short	Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
title_full	Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
title_fullStr	Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
title_full_unstemmed	Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
title_sort	actin cytoskeletal inhibitor 19,20-epoxycytochalasin q sensitizes yeast cells lacking erg6 through actin-targeting and secondarily through disruption of lipid homeostasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/86fbe62d577140e7a6648753ec1e801a
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Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis

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