Defect in dolichol-dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti-fungal drugs

Two temperature-sensitive Saccharomyces cerevisiae mutants, sec59-1 and dpm1-6, impaired, respectively, in dolichol kinase (Sec59p) and dolichyl phosphate mannose (DolPMan) synthase (Dpm1p), have an aberrant cell wall structure and composition. We tested their sensitivity to four classes of antifung...

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Veröffentlicht in:Yeast (Chichester, England) England), 2010-08, Vol.27 (8), p.637-645
Hauptverfasser: Juchimiuk, Mateusz, Pasikowska, Monika, Zatorska, Ewa, Laudy, Agnieszka E, Smoleńska-Sym, Gabriela, Palamarczyk, Grazyna
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container_end_page 645
container_issue 8
container_start_page 637
container_title Yeast (Chichester, England)
container_volume 27
creator Juchimiuk, Mateusz
Pasikowska, Monika
Zatorska, Ewa
Laudy, Agnieszka E
Smoleńska-Sym, Gabriela
Palamarczyk, Grazyna
description Two temperature-sensitive Saccharomyces cerevisiae mutants, sec59-1 and dpm1-6, impaired, respectively, in dolichol kinase (Sec59p) and dolichyl phosphate mannose (DolPMan) synthase (Dpm1p), have an aberrant cell wall structure and composition. We tested their sensitivity to four classes of antifungal drugs used in clinical practice: 5-fluorocytosine, amphotericin B, caspofungin and itraconasole. The strains were resistant to itraconazole and sensitive to the other drugs used. The minimal inhibitory concentration (MIC) of caspofungin and amphotericin B was two-fold lower for sec59-1 and dpm1-6 than for the respective wild-type strains. The sensitivity of both mutants could be brought back to the wild-type level by a multicopy suppressor of the thermosensitive phenotype, the RER2 gene, encoding cis-prenyltransferase involved in dolichol biosynthesis. Biochemical analysis revealed slight changes of the cell wall composition, different in the mutants as compared to the wild-type in response to the drugs. Our data strongly support a relationship between dolichol phosphate level, protein glycosylation and antifungal sensitivity. Copyright © 2010 John Wiley & Sons, Ltd.
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subjects Antifungal Agents - pharmacology
antifungal drugs
cell wall
Cell Wall - chemistry
Cell Wall - ultrastructure
Dimethylallyltranstransferase - biosynthesis
Dimethylallyltranstransferase - genetics
dolichol
Dolichol - metabolism
Gene Expression
Glycoproteins - metabolism
Glycosylation
Hot Temperature
Mannosyltransferases - deficiency
Microbial Sensitivity Tests
Mutation
Phosphotransferases (Alcohol Group Acceptor) - deficiency
Saccharomyces cerevisiae
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - biosynthesis
Saccharomyces cerevisiae Proteins - genetics
title Defect in dolichol-dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti-fungal drugs
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