Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray
Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray
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DOI：
10.1128/aac.45.6.1660-1670.2001
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发表时间：
2001-06-01
影响因子：
4.9
通讯作者：
Vanden Bossche, H
中科院分区：
文献类型：
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作者：
De Backer, MD;Ilyina, T;Vanden Bossche, H
应用全基因组表达谱来确定药物如何实现其治疗效果，为制药业提供了一种令人兴奋的新工具，用于药物作用模式研究。我们使用DNA芯片技术研究了细胞对广谱抗真菌药物伊曲康唑引起的麦角甾醇生物合成干扰的反应。用10微米伊曲康唑处理细胞，同时检测代表整个基因组的6,600多个白色念珠菌基因转录水平，发现296个基因有反应，116个基因转录水平下降至少2.5倍，而180个基因转录水平类似地上升。观察到对唑治疗的反应，ERG基因在全球范围内上调。此外，还观察到ERG6、ERG1、ERG3、ERG4、ERG10、ERG9、ERG26、ERG25、ERC2、IDII、HMG、NCP1和FEN2等与麦角甾醇生物合成有关的基因表达显著上调。本文讨论了伊曲康唑对多种已知代谢过程的影响，因为超过140种功能未知的蛋白质对伊曲康唑有反应，我们的分析可能结合表型数据为其潜在功能提供第一线索。本报告首次描述了应用DNA芯片技术研究一种主要的人类真菌病原体对药物治疗的反应。
The application of genome-wide expression profiling to determine how drugs achieve their therapeutic effect has provided the pharmaceutical industry with an exciting new tool for drug mode-of-action studies. We used DNA chip technology to study cellular responses to perturbations of ergosterol biosynthesis caused by the broad-spectrum antifungal agent itraconazole. Simultaneous examination of over 6,600 Candida albicans gene transcript levels, representing the entire genome, upon treatment of cells with 10 muM itraconazole revealed that 296 genes were responsive, For 116 genes transcript levels were decreased at least 2.5-fold, while for 180 transcript levels were similarly increased. A global upregulation of ERG genes in response to azole treatment was observed. ERG11 and ERGS were found to be upregulated approximately 12-fold, In addition, a significant upregulation was observed for ERG6, ERG1, ERG3, ERG4, ERG10, ERG9, ERG26, ERG25, ERC2, IDII, HMGS, NCP1, and FEN2, all of which are genes known to be involved in ergosterol biosynthesis, The effects of itraconazole on a wide variety of known metabolic processes are discussed, As over 140 proteins with unknown function were responsive to itraconazole, our analysis might provide-in combination with phenotypic data-first hints of their potential function. The present report is the first to describe the application of DNA chip technology to study the response of a major human fungal pathogen to drug treatment.