Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site.
Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site.
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在氟康唑耐药白色念珠菌菌株中，MDR1 编码药物流出决定簇，通过 Mcm1p 结合位点进行转录调控。
DOI：
10.1128/ec.00243-06
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Kumamoto,CarolA
中科院分区：
文献类型：
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作者：
Riggle,PerryJ;Kumamoto,CarolA
Constitutive, high-level transcription of the gene encoding the drug efflux facilitator Mdr1p is commonly observed in laboratory and clinical strains ofCandida albicansthat are resistant to the antifungal drug fluconazole (FLC). In five independently isolated FLCRlaboratory strains, introduction of a wild-typeMDR1promoter fragment fused to the yeast enhanced green fluorescent protein (yEGFP) reporter gene resulted in high-level expression of GFP, demonstrating that overexpression ofMDR1is dependent on atrans-acting factor. This study identified a 35-bpMDR1promoter element, termed the MDRE, that mediates high-levelMDR1transcription. When inserted into a heterologous promoter, the MDRE was sufficient to mediate high-level expression of theyEGFPreporter gene specifically inMDR1 trans-activation strains. The MDRE promoted transcription in an orientation-independent and dosage-dependent manner. Deletion of the MDRE in the full-length promoter did not abolishMDR1 trans-activation, indicating that elements upstream of the MDRE also contribute to transcription ofMDR1in these overexpression strains. Analysis of the MDRE sequence indicated that it contains an Mcm1p binding site very similar in organization to the site seen upstream of theSaccharomyces cerevisiae MFA1andSTE2genes. Electrophoretic mobility shift analysis demonstrated that both wild-type, FLC-sensitive andMDR1 trans-activated, FLC-resistant strains contain a factor that binds the MDRE. Depletion of Mcm1p, by use of a strain in whichMCM1expression is under the control of a regulated promoter (44), resulted in a loss of MDRE binding activity. Thus, the general transcription factor Mcm1p participates in the regulation ofMDR1expression.
