Isolation of Mutants of Candida Glabrata Resistant to Miconazole
Elucidation of the mode of action of azole antifungals would be aided by studying resistant mutants. It is difficult to obtain mutants of Candida albicans in the laboratory, and there have only been a few studies on clinical isolates which seem to be resistant because of impaired drug uptake. C. gla...
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| Veröffentlicht in: | CRC critical reviews in microbiology 1987, Vol.15 (1), p.103-110 |
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| creator | Nicholas, Richard O. Burton, Jacqueline A. Kerridge, David Wayman, Frances J. |
| description | Elucidation of the mode of action of azole antifungals would be aided by studying resistant mutants. It is difficult to obtain mutants of Candida albicans in the laboratory, and there have only been a few studies on clinical isolates which seem to be resistant because of impaired drug uptake. C. glabrata, unlike C. albicans, is haploid and more likely to give rise to resistant variants. Over 30 mutants have been isolated by selection with miconazole on solid medium and have MICs of miconazole about ten times that of the parental strain. One such mutant has a reduced growth rate and final cell yield. In intact cells, ergosterol biosynthesis is tenfold less sensitive to miconazole than in the parent. However, uptake of [3H]miconazole by cells is identical in both strains. The significance of these observations is discussed. |
| doi_str_mv | 10.3109/10408418709104453 |
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It is difficult to obtain mutants of Candida albicans in the laboratory, and there have only been a few studies on clinical isolates which seem to be resistant because of impaired drug uptake. C. glabrata, unlike C. albicans, is haploid and more likely to give rise to resistant variants. Over 30 mutants have been isolated by selection with miconazole on solid medium and have MICs of miconazole about ten times that of the parental strain. One such mutant has a reduced growth rate and final cell yield. In intact cells, ergosterol biosynthesis is tenfold less sensitive to miconazole than in the parent. However, uptake of [3H]miconazole by cells is identical in both strains. The significance of these observations is discussed.</description><identifier>ISSN: 1040-841X</identifier><identifier>ISSN: 0045-6454</identifier><identifier>EISSN: 1549-7828</identifier><identifier>DOI: 10.3109/10408418709104453</identifier><identifier>PMID: 3691159</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Amino Acids - metabolism ; Biological Transport ; Candida - drug effects ; Candida - genetics ; Candida - isolation & purification ; Drug Resistance, Microbial ; Miconazole - metabolism ; Miconazole - pharmacology ; Mutation ; Oxygen Consumption - drug effects ; Spheroplasts - drug effects ; Spheroplasts - metabolism</subject><ispartof>CRC critical reviews in microbiology, 1987, Vol.15 (1), p.103-110</ispartof><rights>1987 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1987</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-f68a2956fa212c97e64c2bc32ff3579e4851f673092fc88b22145c87c809c7143</citedby><cites>FETCH-LOGICAL-c401t-f68a2956fa212c97e64c2bc32ff3579e4851f673092fc88b22145c87c809c7143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/10408418709104453$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/10408418709104453$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>314,776,780,4010,27900,27901,27902,61194,61375</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3691159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicholas, Richard O.</creatorcontrib><creatorcontrib>Burton, Jacqueline A.</creatorcontrib><creatorcontrib>Kerridge, David</creatorcontrib><creatorcontrib>Wayman, Frances J.</creatorcontrib><title>Isolation of Mutants of Candida Glabrata Resistant to Miconazole</title><title>CRC critical reviews in microbiology</title><addtitle>Crit Rev Microbiol</addtitle><description>Elucidation of the mode of action of azole antifungals would be aided by studying resistant mutants. It is difficult to obtain mutants of Candida albicans in the laboratory, and there have only been a few studies on clinical isolates which seem to be resistant because of impaired drug uptake. C. glabrata, unlike C. albicans, is haploid and more likely to give rise to resistant variants. Over 30 mutants have been isolated by selection with miconazole on solid medium and have MICs of miconazole about ten times that of the parental strain. One such mutant has a reduced growth rate and final cell yield. In intact cells, ergosterol biosynthesis is tenfold less sensitive to miconazole than in the parent. However, uptake of [3H]miconazole by cells is identical in both strains. The significance of these observations is discussed.</description><subject>Amino Acids - metabolism</subject><subject>Biological Transport</subject><subject>Candida - drug effects</subject><subject>Candida - genetics</subject><subject>Candida - isolation & purification</subject><subject>Drug Resistance, Microbial</subject><subject>Miconazole - metabolism</subject><subject>Miconazole - pharmacology</subject><subject>Mutation</subject><subject>Oxygen Consumption - drug effects</subject><subject>Spheroplasts - drug effects</subject><subject>Spheroplasts - metabolism</subject><issn>1040-841X</issn><issn>0045-6454</issn><issn>1549-7828</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEYhIMo9fMHeBD25G01ySabBD0oxY9CiyAK3pa3aUJX0k1Nsoj-elNaBBE9ZeCZGfIOQscEn1UEq3OCGZaMSIFVloxXW2iPcKZKIanczjrzMhtedtF-jK8Y45oyPkCDqlaEcLWHrkbRO0it7wpvi0mfoEtxJYfQzdoZFHcOpgESFI8mtnGFi-SLSat9B5_emUO0Y8FFc7R5D9Dz7c3T8L4cP9yNhtfjUjNMUmlrCVTx2gIlVCthaqbpVFfU2ooLZZjkxNaiwopaLeWUUsK4lkJLrLQgrDpAp-veZfBvvYmpWbRRG-egM76PjRCS03xSNpK1UQcfYzC2WYZ2AeGjIbhZrdb8Wi1nTjbl_XRhZt-JzUyZX65521kfFvDug5s1CT6cDzZAp9u4qv67_uJHfG7ApbmGYJpX34cu7_bP574AAS2LCA</recordid><startdate>1987</startdate><enddate>1987</enddate><creator>Nicholas, Richard O.</creator><creator>Burton, Jacqueline A.</creator><creator>Kerridge, David</creator><creator>Wayman, Frances J.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><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></search><sort><creationdate>1987</creationdate><title>Isolation of Mutants of Candida Glabrata Resistant to Miconazole</title><author>Nicholas, Richard O. ; Burton, Jacqueline A. ; Kerridge, David ; Wayman, Frances J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-f68a2956fa212c97e64c2bc32ff3579e4851f673092fc88b22145c87c809c7143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Amino Acids - metabolism</topic><topic>Biological Transport</topic><topic>Candida - drug effects</topic><topic>Candida - genetics</topic><topic>Candida - isolation & purification</topic><topic>Drug Resistance, Microbial</topic><topic>Miconazole - metabolism</topic><topic>Miconazole - pharmacology</topic><topic>Mutation</topic><topic>Oxygen Consumption - drug effects</topic><topic>Spheroplasts - drug effects</topic><topic>Spheroplasts - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nicholas, Richard O.</creatorcontrib><creatorcontrib>Burton, Jacqueline A.</creatorcontrib><creatorcontrib>Kerridge, David</creatorcontrib><creatorcontrib>Wayman, Frances J.</creatorcontrib><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><jtitle>CRC critical reviews in microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nicholas, Richard O.</au><au>Burton, Jacqueline A.</au><au>Kerridge, David</au><au>Wayman, Frances J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isolation of Mutants of Candida Glabrata Resistant to Miconazole</atitle><jtitle>CRC critical reviews in microbiology</jtitle><addtitle>Crit Rev Microbiol</addtitle><date>1987</date><risdate>1987</risdate><volume>15</volume><issue>1</issue><spage>103</spage><epage>110</epage><pages>103-110</pages><issn>1040-841X</issn><issn>0045-6454</issn><eissn>1549-7828</eissn><abstract>Elucidation of the mode of action of azole antifungals would be aided by studying resistant mutants. It is difficult to obtain mutants of Candida albicans in the laboratory, and there have only been a few studies on clinical isolates which seem to be resistant because of impaired drug uptake. C. glabrata, unlike C. albicans, is haploid and more likely to give rise to resistant variants. Over 30 mutants have been isolated by selection with miconazole on solid medium and have MICs of miconazole about ten times that of the parental strain. One such mutant has a reduced growth rate and final cell yield. In intact cells, ergosterol biosynthesis is tenfold less sensitive to miconazole than in the parent. However, uptake of [3H]miconazole by cells is identical in both strains. The significance of these observations is discussed.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>3691159</pmid><doi>10.3109/10408418709104453</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1040-841X |
| ispartof | CRC critical reviews in microbiology, 1987, Vol.15 (1), p.103-110 |
| issn | 1040-841X 0045-6454 1549-7828 |
| language | eng |
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| source | MEDLINE; Taylor & Francis Journals Complete |
| subjects | Amino Acids - metabolism Biological Transport Candida - drug effects Candida - genetics Candida - isolation & purification Drug Resistance, Microbial Miconazole - metabolism Miconazole - pharmacology Mutation Oxygen Consumption - drug effects Spheroplasts - drug effects Spheroplasts - metabolism |
| title | Isolation of Mutants of Candida Glabrata Resistant to Miconazole |
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