Source:http://linkedlifedata.com/resource/pubmed/id/20223895
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 7
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pubmed:dateCreated |
2010-6-18
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1473-5644
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
797-803
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pubmed:meshHeading |
pubmed-meshheading:20223895-Antifungal Agents,
pubmed-meshheading:20223895-Candida albicans,
pubmed-meshheading:20223895-DNA Topoisomerases, Type II,
pubmed-meshheading:20223895-Drug Resistance, Fungal,
pubmed-meshheading:20223895-Ergosterol,
pubmed-meshheading:20223895-Fungal Proteins,
pubmed-meshheading:20223895-Gene Expression Regulation, Fungal,
pubmed-meshheading:20223895-Microbial Sensitivity Tests,
pubmed-meshheading:20223895-Mutation
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pubmed:year |
2010
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pubmed:articleTitle |
TOP2 gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Candida albicans.
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pubmed:affiliation |
Department of Pharmacology, China Pharmaceutical University, Nanjing, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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