Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China.
Curr Microbiol. 2012 Jun;64(6):530-8. doi: 10.1007/s00284-012-0104-9. Epub 2012 Mar 3.
Tuberculosis (TB) is still one of the most common causes of death in the world. The emergence of multidrug-resistant and extensively drug-resistant (XDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has increased the importance of searching for alternative targets to develop new antimycobacterial drugs. Linezolid, the first of oxazolidinones, is active in vitro against M. tuberculosis, but the response mechanisms of M. tuberculosis to linezolid are still poorly understood. To reveal the possible mechanism of action of linezolid against M. tuberculosis, commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes triggered by treatment with subinhibitory concentrations of linezolid. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. A total of 729 genes were found to be differentially regulated by linezolid. Among these, 318 genes were upregulated, and 411 genes were downregulated. A number of important genes were significantly regulated that are involved in various pathways, such as protein synthesis, sulfite metabolism, and genes involved in the cell envelope and virulence. This genome-wide transcriptomics approach produced the first insights into the response of M. tuberculosis to a linezolid challenge.
结核病（TB）仍然是世界上最常见的死亡原因之一。耐多药和广泛耐药（XDR-TB）结核分枝杆菌（M. tuberculosis）菌株的出现增加了寻找替代靶标开发新抗分枝杆菌药物的重要性。利奈唑胺是第一个噁唑烷酮类药物，在体外对 M. tuberculosis 具有活性，但 M. tuberculosis 对利奈唑胺的反应机制仍知之甚少。为了揭示利奈唑胺对 M. tuberculosis 的可能作用机制，使用商业寡核苷酸微阵列分析了亚抑菌浓度利奈唑胺处理触发的全基因组转录变化。对选定基因进行了定量实时 RT-PCR 以验证微阵列结果。发现 729 个基因被利奈唑胺差异调控。其中，318 个基因上调，411 个基因下调。许多重要的基因被显著调控，涉及多种途径，如蛋白质合成、亚硫酸盐代谢以及与细胞包膜和毒力相关的基因。这种全基因组转录组学方法首次深入了解了 M. tuberculosis 对利奈唑胺挑战的反应。
