The Differential Gene Expression Pattern of Mycobacterium tuberculosis in Response to Capreomycin and PA-824 versus First-Line TB Drugs Reveals Stress- and PE/PPE-Related Drug Targets.
The Differential Gene Expression Pattern of Mycobacterium tuberculosis in Response to Capreomycin and PA-824 versus First-Line TB Drugs Reveals Stress- and PE/PPE-Related Drug Targets.
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DOI：
10.1155/2009/879621
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发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Tai, Shu C
中科院分区：
文献类型：
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作者：
Fu, Li M;Tai, Shu C
结核病是一种主要传染病，每年导致数百万人死亡。如何根除分枝杆菌的持续存在已成为开发下一代结核病药物的中心研究重点。然而，这一领域的知识基本上是有限的，只有少数药物，特别是卷曲霉素和 PA-824，已被证明对非复制性持续性结核杆菌具有活性。在本研究中，我们对从公共领域获得的基于微阵列的基因表达数据进行了新的生物信息学分析，以探索卷曲霉素和 PA-824 组与主要为一线结核病药物组之间药物差异诱导的基因。我们的研究已鉴定出 42 个由卷曲霉素和 PA-824 特异性诱导的基因。其中许多基因与应激反应有关。就特定类别中已识别基因相对于整个基因组的分布而言，只有PE/PPE和保守假设类别具有统计显着性。本研究中确定的 42 个基因中有 6 个位于结核病结构基因组学联盟选出的前 100 个持久性目标的列表中。有必要进一步生物学阐明它们在分枝杆菌持久性中的作用。
Tuberculosis is a leading infectious disease causing millions of deaths each year. How to eradicate mycobacterial persistence has become a central research focus for developing next-generation TB drugs. Yet, the knowledge in this area is fundamentally limited and only a few drugs, notably capreomycin and PA-824, have been shown to be active against non-replicating persistent TB bacilli. In this study, we performed a new bioinformatics analysis on microarray-based gene expression data obtained from the public domain to explore genes that were differentially induced by drugs between the group of capreomycin and PA-824 and the group of mainly the first-line TB drugs. Our study has identified 42 genes specifically induced by capreomycin and PA-824. Many of these genes are related to stress responses. In terms of the distribution of identified genes in a specific category relative to the whole genome, only the categories of PE/PPE and conserved hypotheticals have statistical significance. Six among the 42 genes identified in this study are on the list of the top 100 persistence targets selected by the TB Structural Genomics Consortium. Further biological elucidation of their roles in mycobacterial persistence is warranted.