Linked Life Data

2556119

Source:http://linkedlifedata.com/resource/pubmed/id/2556119

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-12-28
pubmed:abstractText
Two azole resistant isolates of Saccharomyces cerevisiae carried mutations allelic to erg 3 and were blocked to differing degrees at the C5-6 desaturation step of ergosterol biosynthesis. When treated with the sterol 14 alpha-demethylation inhibitor fluconazole the wild-type sensitive strain accumulated lanosterol and 14 alpha-methyl-erogosta-8,24(28)-dien-3 beta, 6 alpha-diol (14-methyl-3,6 diol). The stringent desaturase mutant, A2, accumulated 14 alpha-methyl-8,24(28)-dien-3 beta-ol (14-methyl fecosterol) and lanosterol as the major sterol components when treated with fluconazole. Resistant isolate A3 accumulated 14-methyl-3,6-diol, 14-methyl fecosterol, and lanosterol and was only partially blocked at sterol C5-6 desaturation. We conclude that functional sterol C5-6 desaturase is required for the synthesis of 14-methyl-3,6-diol under conditions of azole inhibition. We present a new hypothesis for the mode of action of azole antifungals based on the inability of 14-methyl-3,6-diol to support growth, and suggest that growth can occur through utilisation of 14-methyl fecosterol, produced by a combination of azole inhibition and defective sterol C5-6 desaturation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1170-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Defective sterol C5-6 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals.
pubmed:affiliation
University Department of Pharmacology and Therapeutics, Sheffield University, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't