Wei Jian, Liang Junchao, Shi Qiyun, Yuan Peng, Meng Rizeng, Tang Xudong, Yu Lu, Guo Na
Life Science Department ChangChun Normal University Changchun P.R. China ; Bio-Reactor Center Jilin Agrichultural University Changchun P.R. China.
Department of Food Quality and Safety Key Laboratory of Zoonosis Research Institute of Zoonosis Ministry of Education Changchun P. R. China.
Braz J Microbiol. 2014 Apr 18;45(1):333-41. doi: 10.1590/S1517-83822014005000032. eCollection 2014.
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, still causes higher mortality than any other bacterial pathogen until now. With the emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR-TB) strains, it becomes more important to search for alternative targets to develop new antimycobacterial drugs. Lupulone is a compound extracted from Hops (Hurnulus lupulus), which exhibits a good antimicrobial activity against M. tuberculosis with minimal inhibitory concentration (MIC) value of 10 μg/mL, but the response mechanisms of lupulone against M. tuberculosis are still poorly understood. In this study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to MIC of lupulone. A total of 540 genes were found to be differentially regulated by lupulone. Of these, 254 genes were upregulated, and 286 genes were downregulated. A number of important genes were significantly regulated which are involved in various pathways, such as surface-exposed lipids, cytochrome P450 enzymes, PE/PPE multigene families, ABC transporters, and protein synthesis. Real-time quantitative RT-PCR was performed for choosed genes to verified the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis to a lupulone challenge.
结核分枝杆菌（M. tuberculosis）是结核病的病原体，迄今为止，其致死率仍高于其他任何细菌病原体。随着耐多药（MDR）和广泛耐药（XDR-TB）菌株的出现和传播，寻找新的抗分枝杆菌药物的替代靶点变得更加重要。蛇麻酮是一种从啤酒花（Humulus lupulus）中提取的化合物，对结核分枝杆菌具有良好的抗菌活性，最低抑菌浓度（MIC）值为10μg/mL，但蛇麻酮对结核分枝杆菌的作用机制仍知之甚少。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麻酮MIC时引发的结核分枝杆菌H37Rv的整体转录反应。共发现540个基因受到蛇麻酮的差异调节。其中，254个基因上调，286个基因下调。一些重要基因受到显著调节，它们参与各种途径，如表面暴露脂质、细胞色素P450酶、PE/PPE多基因家族、ABC转运蛋白和蛋白质合成。对选定基因进行实时定量RT-PCR以验证微阵列结果。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对蛇麻酮挑战的反应。
