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 |
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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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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.</description><identifier>ISSN: 0749-503X</identifier><identifier>ISSN: 1097-0061</identifier><identifier>EISSN: 1097-0061</identifier><identifier>DOI: 10.1002/yea.1803</identifier><identifier>PMID: 20602334</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>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</subject><ispartof>Yeast (Chichester, England), 2010-08, Vol.27 (8), p.637-645</ispartof><rights>Copyright © 2010 John Wiley & Sons, Ltd.</rights><rights>Copyright (c) 2010 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4083-bae9a0d127c6a8d13021819b2a4980ce79bcc917b350349e9424d8053708493d3</citedby><cites>FETCH-LOGICAL-c4083-bae9a0d127c6a8d13021819b2a4980ce79bcc917b350349e9424d8053708493d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fyea.1803$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fyea.1803$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20602334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Juchimiuk, Mateusz</creatorcontrib><creatorcontrib>Pasikowska, Monika</creatorcontrib><creatorcontrib>Zatorska, Ewa</creatorcontrib><creatorcontrib>Laudy, Agnieszka E</creatorcontrib><creatorcontrib>Smoleńska-Sym, Gabriela</creatorcontrib><creatorcontrib>Palamarczyk, Grazyna</creatorcontrib><title>Defect in dolichol-dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti-fungal drugs</title><title>Yeast (Chichester, England)</title><addtitle>Yeast</addtitle><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.</description><subject>Antifungal Agents - pharmacology</subject><subject>antifungal drugs</subject><subject>cell wall</subject><subject>Cell Wall - chemistry</subject><subject>Cell Wall - ultrastructure</subject><subject>Dimethylallyltranstransferase - biosynthesis</subject><subject>Dimethylallyltranstransferase - genetics</subject><subject>dolichol</subject><subject>Dolichol - metabolism</subject><subject>Gene Expression</subject><subject>Glycoproteins - metabolism</subject><subject>Glycosylation</subject><subject>Hot Temperature</subject><subject>Mannosyltransferases - deficiency</subject><subject>Microbial Sensitivity Tests</subject><subject>Mutation</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - deficiency</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - biosynthesis</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><issn>0749-503X</issn><issn>1097-0061</issn><issn>1097-0061</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQQC0EoktB4heAb3BJGX9sbB-rUj6kShxKJThZjj3ZGnnjxU62yr8nq124ocqHOfjpSTOPkNcMLhgA_zCju2AaxBOyYmBUA9Cyp2QFSppmDeLHGXlR6y8AxtZcPydnHFrgQsgV2X_EHv1I40BDTtHf59QE3OEQcBjpJs0-1zm5MeZhYXxBV7HSikONY9zHcaa5p7fO-3tX8nb2y6fHgvtYo0M65gdXQqVuGGPTT8PGJRrKtKkvybPepYqvTvOc3H26_n71pbn59vnr1eVN4yVo0XQOjYPAuPKt04EJ4Ewz03EnjQaPynTeG6Y6sWwpDRrJZdCwFgq0NCKIc_Lu6N2V_HvCOtptrB5TcgPmqVqtBTClhHqcVJwJyYR-lFRSmxYEPzjfH0lfcq0Fe7srcevKbBnYQzi7hLOHcAv65iSdui2Gf-DfUgvQHIGHmHD-r8j-vL48Cd8e-d5l6zYlVnt3y2E5IdNqea34A-Qfq7g</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Juchimiuk, Mateusz</creator><creator>Pasikowska, Monika</creator><creator>Zatorska, Ewa</creator><creator>Laudy, Agnieszka E</creator><creator>Smoleńska-Sym, Gabriela</creator><creator>Palamarczyk, Grazyna</creator><general>John Wiley & Sons, Ltd</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>M7N</scope></search><sort><creationdate>201008</creationdate><title>Defect in dolichol-dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti-fungal drugs</title><author>Juchimiuk, Mateusz ; Pasikowska, Monika ; Zatorska, Ewa ; Laudy, Agnieszka E ; Smoleńska-Sym, Gabriela ; Palamarczyk, Grazyna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4083-bae9a0d127c6a8d13021819b2a4980ce79bcc917b350349e9424d8053708493d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Antifungal Agents - pharmacology</topic><topic>antifungal drugs</topic><topic>cell wall</topic><topic>Cell Wall - chemistry</topic><topic>Cell Wall - ultrastructure</topic><topic>Dimethylallyltranstransferase - biosynthesis</topic><topic>Dimethylallyltranstransferase - genetics</topic><topic>dolichol</topic><topic>Dolichol - metabolism</topic><topic>Gene Expression</topic><topic>Glycoproteins - metabolism</topic><topic>Glycosylation</topic><topic>Hot Temperature</topic><topic>Mannosyltransferases - deficiency</topic><topic>Microbial Sensitivity Tests</topic><topic>Mutation</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - deficiency</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - biosynthesis</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Juchimiuk, Mateusz</creatorcontrib><creatorcontrib>Pasikowska, Monika</creatorcontrib><creatorcontrib>Zatorska, Ewa</creatorcontrib><creatorcontrib>Laudy, Agnieszka E</creatorcontrib><creatorcontrib>Smoleńska-Sym, Gabriela</creatorcontrib><creatorcontrib>Palamarczyk, Grazyna</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Yeast (Chichester, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Juchimiuk, Mateusz</au><au>Pasikowska, Monika</au><au>Zatorska, Ewa</au><au>Laudy, Agnieszka E</au><au>Smoleńska-Sym, Gabriela</au><au>Palamarczyk, Grazyna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defect in dolichol-dependent glycosylation increases sensitivity of Saccharomyces cerevisiae towards anti-fungal drugs</atitle><jtitle>Yeast (Chichester, England)</jtitle><addtitle>Yeast</addtitle><date>2010-08</date><risdate>2010</risdate><volume>27</volume><issue>8</issue><spage>637</spage><epage>645</epage><pages>637-645</pages><issn>0749-503X</issn><issn>1097-0061</issn><eissn>1097-0061</eissn><abstract>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.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>20602334</pmid><doi>10.1002/yea.1803</doi><tpages>9</tpages></addata></record> |
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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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