Life Science Department, Chang Chun Normal University, Changchun 130062, China.
Pol J Microbiol. 2013;62(1):23-30.
Tuberculosis (TB), affecting one-third of the global population, kills an estimated two to three million people every year. The development of drug resistance is becoming a serious threat to any attempt to control this disease, which underscores the need for new agents targeting Mycobacterium tuberculosis (M. tuberculosis). Osthole (7-methoxy-8-isopentenoxycoumarin) is a coumarin derivative present in many medicinal plants. Previous studies have shown that osthole possesses antimycobacterial effects, however, the action mechanism of osthole is unclear. In the study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to osthole. Analysis of the microarray data revealed that a total of 478 genes were differentially regulated by osthole. Of these, 241 genes were upregulated, and 237 genes were downregulated. Some of the important genes that were significantly regulated are related to different pathways such as fumarate reductase, class I peroxidase, cell wall, nitrate respiration, and protein synthesis. Real-time quantitative RT-PCR was performed for chosen genes to validate the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis when exposed to osthole.
结核病(TB)影响了全球三分之一的人口,每年估计有 200 至 300 万人因此死亡。耐药性的发展正对任何控制这种疾病的尝试构成严重威胁,这凸显了需要针对结核分枝杆菌(M. tuberculosis)的新型药物。蛇床子素(7-甲氧基-8-异戊烯氧基香豆素)是许多药用植物中的一种香豆素衍生物。先前的研究表明,蛇床子素有抗分枝杆菌的作用,然而,其作用机制尚不清楚。在本研究中,我们使用商业寡核苷酸微阵列来确定暴露于蛇床子素后结核分枝杆菌 H37Rv 的全转录反应。微阵列数据分析显示,蛇床子素总共调节了 478 个基因。其中,241 个基因上调,237 个基因下调。一些重要的基因,如延胡索酸还原酶、I 类过氧化物酶、细胞壁、硝酸盐呼吸和蛋白质合成,它们的表达水平显著受到调控。为了验证微阵列结果,我们对选定的基因进行了实时定量 RT-PCR。据我们所知,这种全基因组转录组学方法首次揭示了结核分枝杆菌暴露于蛇床子素时的反应。