1887

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Volume 59, Issue 7

gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Free

Abstract

In this study the role of the gene in fungal drug susceptibility was investigated by disrupting and overexpressing the gene in . MIC determination and a spot assay showed that a Δ/Δ 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 2 did not influence the activity of drug efflux pumps. Sterol analysis with GC/high-resolution MS indicated that the intracellular ergosterol composition of the Δ/Δ 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 gene, an essential gene in ergosterol biosynthesis, was upregulated. These results demonstrate a close relationship between the gene and drug susceptibility in .

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): HRMS, high-resolution MS
SGM
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2010-07-01
2024-04-23
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TOP2 gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Candida albicans
J. Med. Microbiol. 59, 797 (2010); https://doi.org/10.1099/jmm.0.018325-0
/content/journal/jmm/10.1099/jmm.0.018325-0
/content/journal/jmm/10.1099/jmm.0.018325-0
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