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Defect in dolichol‐dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti‐fungal drugs
Author(s) -
Juchimiuk Mateusz,
Pasikowska Monika,
Zatorska Ewa,
Laudy Agnieszka E.,
SmoleńskaSym Gabriela,
Palamarczyk Grazyna
Publication year - 2010
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.1803
Subject(s) - dolichol , caspofungin , biology , saccharomyces cerevisiae , mutant , mannose , biochemistry , wild type , antifungal drug , glycosylation , gene , amphotericin b , microbiology and biotechnology , biosynthesis , antifungal
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.