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首页> 外文期刊>Eukaryotic cell >Transcriptional Regulation of MDR1, Encoding a Drug Efflux Determinant, in Fluconazole-Resistant Candida albicans Strains through an Mcm1p Binding Site
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Transcriptional Regulation of MDR1, Encoding a Drug Efflux Determinant, in Fluconazole-Resistant Candida albicans Strains through an Mcm1p Binding Site

机译：通过Mcm1p结合位点在耐氟康唑的白色念珠菌菌株中编码药物外排决定因子的MDR1的转录调控。

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Constitutive, high-level transcription of the gene encoding the drug efflux facilitator Mdr1p is commonly observed in laboratory and clinical strains of Candida albicans that are resistant to the antifungal drug fluconazole (FLC). In five independently isolated FLCR laboratory strains, introduction of a wild-type MDR1 promoter fragment fused to the yeast enhanced green fluorescent protein (yEGFP) reporter gene resulted in high-level expression of GFP, demonstrating that overexpression of MDR1 is dependent on a trans-acting factor. This study identified a 35-bp MDR1 promoter element, termed the MDRE, that mediates high-level MDR1 transcription. When inserted into a heterologous promoter, the MDRE was sufficient to mediate high-level expression of the yEGFP reporter gene specifically in MDR1 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 abolish MDR1 trans-activation, indicating that elements upstream of the MDRE also contribute to transcription of MDR1 in 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 the Saccharomyces cerevisiae MFA1 and STE2 genes. Electrophoretic mobility shift analysis demonstrated that both wild-type, FLC-sensitive and MDR1 trans-activated, FLC-resistant strains contain a factor that binds the MDRE. Depletion of Mcm1p, by use of a strain in which MCM1 expression 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 of MDR1 expression.
机译：在实验室和临床上对抗真菌药物氟康唑（FLC）的白色念珠菌（Candida albicans）菌株中普遍观察到编码药物外流促进剂Mdr1p的基因的组成型高水平转录。在五个独立分离的FLC R 实验室菌株中，引入与酵母增强的绿色荧光蛋白（ yEGFP ）融合的野生型 MDR1 启动子片段。报告基因导致GFP的高水平表达，证明 MDR1 的过表达取决于 trans-作用因子。这项研究确定了一个35 bp的 MDR1 启动子元件，称为MDRE，可介导高水平的 MDR1 转录。当插入异源启动子时，MDRE足以介导 yEGFP 报告基因在 MDR1反转录激活菌株中的高水平表达。 MDRE以方向独立和剂量依赖的方式促进转录。在全长启动子中删除MDRE不会消除 MDR1 激活，这表明MDRE上游的元件在这些过表达菌株中也有助于 MDR1 的转录。对MDRE序列的分析表明，它含有一个Mcm1p结合位点，该结合位点的组织结构与啤酒酵母MFA1 和 STE2 基因上游的位置非常相似。电泳迁移率变动分析表明，野生型，对FLC敏感的和对 DRM反转录激活的，对FLC耐药的菌株均包含与MDRE结合的因子。通过使用其中 MCM1 表达受调控的启动子控制的菌株，Mcm1p耗竭，导致MDRE结合活性丧失。因此，一般转录因子Mcm1p参与了 MDR1 表达的调控。

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