Overexpression of PDR16 confers resistance to complex sphingolipid biosynthesis inhibitor aureobasidin A in yeast Saccharomyces cerevisiae

Yuka Katsuki, Yutaro Yamaguchi, Motohiro Tani

Research output: Contribution to journalArticle

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 languageEnglish
Article numberfnx255
JournalFEMS microbiology letters
Volume365
Issue number3
DOIs
Publication statusPublished - Feb 1 2018

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Overexpression of PDR16 confers resistance to complex sphingolipid biosynthesis inhibitor aureobasidin A in yeast Saccharomyces cerevisiae'. Together they form a unique fingerprint.

  • Cite this