A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy

Abstract The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA) protects plants, mammals and humans effectively against various fungal pathogens. However, the mechanism by which PCA inhibits or kills fungal pathogens is not fully understood. We analyzed the effects of PCA on the g...

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Autores principales:	Xiaolong Zhu, Yan Zeng, Xiu Zhao, Shenshen Zou, Ya-Wen He, Yongheng Liang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fdce925e30184a618d7734c5f572b008
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spelling	oai:doaj.org-article:fdce925e30184a618d7734c5f572b0082021-12-02T16:06:15ZA genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy10.1038/s41598-017-01452-62045-2322https://doaj.org/article/fdce925e30184a618d7734c5f572b0082017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01452-6https://doaj.org/toc/2045-2322Abstract The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA) protects plants, mammals and humans effectively against various fungal pathogens. However, the mechanism by which PCA inhibits or kills fungal pathogens is not fully understood. We analyzed the effects of PCA on the growth of two fungal model organisms, Saccharomyces cerevisiae and Candida albicans, and found that PCA inhibited yeast growth in a dose-dependent manner which was inversely dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in a dose-dependent manner as pH increased. We then screened a yeast mutant library to identify genes whose mutation or deletion conferred resistance or sensitivity to PCA. We isolated 193 PCA-resistant or PCA-sensitive mutants in clusters, including vesicle-trafficking- and autophagy-defective mutants. Further analysis showed that unlike hygromycin B, PCA significantly altered intracellular vesicular trafficking under growth conditions and blocked autophagy under starvation conditions. These results suggest that PCA inhibits or kills pathogenic fungi in a complex way, in part by disrupting vesicular trafficking and autophagy.Xiaolong ZhuYan ZengXiu ZhaoShenshen ZouYa-Wen HeYongheng LiangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaolong Zhu Yan Zeng Xiu Zhao Shenshen Zou Ya-Wen He Yongheng Liang A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
description	Abstract The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA) protects plants, mammals and humans effectively against various fungal pathogens. However, the mechanism by which PCA inhibits or kills fungal pathogens is not fully understood. We analyzed the effects of PCA on the growth of two fungal model organisms, Saccharomyces cerevisiae and Candida albicans, and found that PCA inhibited yeast growth in a dose-dependent manner which was inversely dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in a dose-dependent manner as pH increased. We then screened a yeast mutant library to identify genes whose mutation or deletion conferred resistance or sensitivity to PCA. We isolated 193 PCA-resistant or PCA-sensitive mutants in clusters, including vesicle-trafficking- and autophagy-defective mutants. Further analysis showed that unlike hygromycin B, PCA significantly altered intracellular vesicular trafficking under growth conditions and blocked autophagy under starvation conditions. These results suggest that PCA inhibits or kills pathogenic fungi in a complex way, in part by disrupting vesicular trafficking and autophagy.
format	article
author	Xiaolong Zhu Yan Zeng Xiu Zhao Shenshen Zou Ya-Wen He Yongheng Liang
author_facet	Xiaolong Zhu Yan Zeng Xiu Zhao Shenshen Zou Ya-Wen He Yongheng Liang
author_sort	Xiaolong Zhu
title	A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
title_short	A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
title_full	A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
title_fullStr	A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
title_full_unstemmed	A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
title_sort	genetic screen in combination with biochemical analysis in saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fdce925e30184a618d7734c5f572b008
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A genetic screen in combination with biochemical analysis in Saccharomyces cerevisiae indicates that phenazine-1-carboxylic acid is harmful to vesicular trafficking and autophagy

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