Abstract
Sphingolipids are essential for normal cell growth of yeast Saccharomyces cerevisiae. Aureobasidin A (AbA), an antifungal drug, inhibits Aur1, an enzyme catalyzing the synthesis of inositol phosphorylceramide, and induces a strong growth defect in yeast. In this study, we screened for multicopy suppressor genes that confer resistance to AbA, and identified PDR16. In addition, it was found that PDR17, a paralog of PDR16, also functions as a multicopy suppressor. Pdr16 and Pdr17 belong to a family of phosphatidylinositol transfer proteins; however, cells overexpressing the other members of the family hardly exhibited resistance to AbA. Overexpression of a lipid-binding defective mutant of Pdr16 did not confer the resistance to AbA, indicating that the lipid-binding activity is essential for acquiring resistance to AbA. When expression of the AUR1 gene was repressed by a tetracycline-regulatable promoter, the overexpression of PDR16 or PDR17 did not suppress the growth defect caused by the AUR1 repression. Quantification analysis of complex sphingolipids revealed that in AbA-treated cells, but not in cells in which AUR1 was repressed by the tetracycline-regulatable promoter, the reductions of complex sphingolipid levels were suppressed by the overexpressed PDR16. Thus, it was indicated that the overexpression of PDR16 reduces the effectiveness of AbA against intracellular Aur1 activity.
| Original language | English |
|---|---|
| Article number | fnx255 |
| Journal | FEMS microbiology letters |
| Volume | 365 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 1 2018 |
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All Science Journal Classification (ASJC) codes
- Microbiology
- Molecular Biology
- Genetics
Cite this
Overexpression of PDR16 confers resistance to complex sphingolipid biosynthesis inhibitor aureobasidin A in yeast Saccharomyces cerevisiae. / Katsuki, Yuka; Yamaguchi, Yutaro; Tani, Motohiro.
In: FEMS microbiology letters, Vol. 365, No. 3, fnx255, 01.02.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of PDR16 confers resistance to complex sphingolipid biosynthesis inhibitor aureobasidin A in yeast Saccharomyces cerevisiae
AU - Katsuki, Yuka
AU - Yamaguchi, Yutaro
AU - Tani, Motohiro
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Sphingolipids are essential for normal cell growth of yeast Saccharomyces cerevisiae. Aureobasidin A (AbA), an antifungal drug, inhibits Aur1, an enzyme catalyzing the synthesis of inositol phosphorylceramide, and induces a strong growth defect in yeast. In this study, we screened for multicopy suppressor genes that confer resistance to AbA, and identified PDR16. In addition, it was found that PDR17, a paralog of PDR16, also functions as a multicopy suppressor. Pdr16 and Pdr17 belong to a family of phosphatidylinositol transfer proteins; however, cells overexpressing the other members of the family hardly exhibited resistance to AbA. Overexpression of a lipid-binding defective mutant of Pdr16 did not confer the resistance to AbA, indicating that the lipid-binding activity is essential for acquiring resistance to AbA. When expression of the AUR1 gene was repressed by a tetracycline-regulatable promoter, the overexpression of PDR16 or PDR17 did not suppress the growth defect caused by the AUR1 repression. Quantification analysis of complex sphingolipids revealed that in AbA-treated cells, but not in cells in which AUR1 was repressed by the tetracycline-regulatable promoter, the reductions of complex sphingolipid levels were suppressed by the overexpressed PDR16. Thus, it was indicated that the overexpression of PDR16 reduces the effectiveness of AbA against intracellular Aur1 activity.
AB - Sphingolipids are essential for normal cell growth of yeast Saccharomyces cerevisiae. Aureobasidin A (AbA), an antifungal drug, inhibits Aur1, an enzyme catalyzing the synthesis of inositol phosphorylceramide, and induces a strong growth defect in yeast. In this study, we screened for multicopy suppressor genes that confer resistance to AbA, and identified PDR16. In addition, it was found that PDR17, a paralog of PDR16, also functions as a multicopy suppressor. Pdr16 and Pdr17 belong to a family of phosphatidylinositol transfer proteins; however, cells overexpressing the other members of the family hardly exhibited resistance to AbA. Overexpression of a lipid-binding defective mutant of Pdr16 did not confer the resistance to AbA, indicating that the lipid-binding activity is essential for acquiring resistance to AbA. When expression of the AUR1 gene was repressed by a tetracycline-regulatable promoter, the overexpression of PDR16 or PDR17 did not suppress the growth defect caused by the AUR1 repression. Quantification analysis of complex sphingolipids revealed that in AbA-treated cells, but not in cells in which AUR1 was repressed by the tetracycline-regulatable promoter, the reductions of complex sphingolipid levels were suppressed by the overexpressed PDR16. Thus, it was indicated that the overexpression of PDR16 reduces the effectiveness of AbA against intracellular Aur1 activity.
UR - http://www.scopus.com/inward/record.url?scp=85056590939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056590939&partnerID=8YFLogxK
U2 - 10.1093/femsle/fnx255
DO - 10.1093/femsle/fnx255
M3 - Article
C2 - 29240942
AN - SCOPUS:85056590939
VL - 365
JO - FEMS Microbiology Letters
JF - FEMS Microbiology Letters
SN - 0378-1097
IS - 3
M1 - fnx255
ER -