An MDR1 promoter allele with higher promoter activity is common in clinically isolated strains of Candida albicans.
An MDR1 promoter allele with higher promoter activity is common in clinically isolated strains of Candida albicans.
复制标题
具有较高启动子活性的 MDR1 启动子等位基因在临床分离的白色念珠菌菌株中很常见。
DOI：
10.1007/s00438-011-0650-z
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kumamoto,CarolA
中科院分区：
文献类型：
--
作者：
Bruzual,Igor;Kumamoto,CarolA
In the opportunistic fungal pathogenCandida albicans, up-regulation ofMDR1, encoding an efflux transporter, leads to increased resistance to the antifungal drug fluconazole. Antifungal resistance has been linked to several types of genetic change inC. albicans, including changes in genome structure, genetic alteration of the drug target, and overexpression of transporters. High-level over-expression ofMDR1is commonly mediated by mutation in atrans-acting factor, Mrr1p. This report describes a second mechanism that contributes to up-regulation ofMDR1expression. By analyzing the sequence of theMDR1promoter region in fluconazole-resistant and fluconazole-susceptible strains, we identified sequence polymorphisms that defined two linkage groups, corresponding to the two alleles in the diploid genome. One of the alleles conferred higherMDR1expression compared with the other allele. Strains in which both alleles were of the higher activity type were common in collections of clinically isolated strains while strains carrying only the less active allele were rare. As increased expression ofMDR1confers higher resistance to drugs, strains with the more activeMDR1promoter allele may grow or survive longer when exposed to drugs or other selective pressures, providing greater opportunity for mutations that confer high-level drug resistance to arise. Through this mechanism, higher activity alleles of theMDR1promoter could promote the development of drug resistance.
