Fu Li M, Tai Shu C
Pacific Tuberculosis and Cancer Research Organization, P. O. Box 9706, Anaheim, CA 92812, USA.
Int J Microbiol. 2009;2009:879621. doi: 10.1155/2009/879621. Epub 2009 Jul 22.
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.
结核病是一种主要的传染病，每年导致数百万人死亡。如何消除分枝杆菌的持续性已成为开发下一代抗结核药物的核心研究重点。然而，该领域的知识从根本上来说是有限的，只有少数几种药物，特别是卷曲霉素和PA-824，已被证明对非复制性持续结核杆菌有活性。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，以探索在卷曲霉素和PA-824组与主要是一线抗结核药物组之间药物差异诱导的基因。我们的研究确定了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。就已鉴定基因在相对于整个基因组的特定类别中的分布而言，只有PE/PPE和保守假设类别具有统计学意义。本研究中鉴定的42个基因中有6个在结核病结构基因组学联盟选择的前100个持续性靶点列表中。有必要对它们在分枝杆菌持续性中的作用进行进一步的生物学阐释。
