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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 7
pubmed:dateCreated
2010-6-18
pubmed:abstractText
In this study the role of the TOP2 gene in fungal drug susceptibility was investigated by disrupting and overexpressing the gene in Candida albicans. MIC determination and a spot assay showed that a top2Delta/Delta null mutant (strain T2bc) was more resistant to the antifungals tested than the wild-type (strain CAI4). Real-time RT-PCR and rhodamine 6G efflux examination showed that TOP2 did not influence the activity of drug efflux pumps. Sterol analysis with GC/high-resolution MS indicated that the intracellular ergosterol composition of the top2Delta/Delta mutant was significantly increased. Subsequently, fluorescence polarization measurements also revealed that Top2-deprived cells displayed a decrease in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Quantitative real-time RT-PCR analysis further confirmed that the ERG11 gene, an essential gene in ergosterol biosynthesis, was upregulated. These results demonstrate a close relationship between the TOP2 gene and drug susceptibility in C. albicans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1473-5644
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
797-803
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
TOP2 gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Candida albicans.
pubmed:affiliation
Department of Pharmacology, China Pharmaceutical University, Nanjing, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't