Fu Li M, Shinnick Thomas M
Pacific Tuberculosis and Cancer Research Organization, 8 Corporate Park, Suite 300, Irvine, CA 92606, USA.
J Infect. 2007 Mar;54(3):277-84. doi: 10.1016/j.jinf.2006.05.012. Epub 2006 Jul 5.
Multi-drug resistance and latent infection are two major issues in current tuberculosis (TB) control and management. Capreomycin is an important drug used for TB with multi-drug resistance. A recent study also indicates that this drug possesses unique bactericidal activity against non-replicating TB bacilli among known anti-TB drugs. Thus, there is an urgent need for investigating the full-spectrum action of capreomycin.
Here we conduct the first microarray-based study on capreomycin using the high-resolution Affymetrix oligonucleotide GeneChip system.
The results indicate that capreomycin primarily acts on the information pathways but it also significantly affects cell wall, cell processes, intermediate metabolism and respiration in Mycobacterium tuberculosis.
This study not only transcriptionally validates the specific molecular target, 16S rRNA, but also discovers potential new targets of capreomycin, including genes operating at the DNA level, such as Rv0054 (ssb) and Rv3715c (recR), as well as genes involved in cell division like Rv3260c (whiB2). In addition, the nuo gene cluster and the ATP synthase gene cluster are repressed.
多重耐药和潜伏感染是当前结核病防控中的两个主要问题。卷曲霉素是用于治疗多重耐药结核病的一种重要药物。最近一项研究还表明，在已知抗结核药物中，该药物对非复制型结核杆菌具有独特的杀菌活性。因此，迫切需要研究卷曲霉素的全谱作用。
在此，我们使用高分辨率的Affymetrix寡核苷酸基因芯片系统对卷曲霉素进行了首次基于微阵列的研究。
结果表明，卷曲霉素主要作用于信息通路，但也显著影响结核分枝杆菌的细胞壁、细胞过程、中间代谢和呼吸作用。
本研究不仅在转录水平验证了特定分子靶点16S rRNA，还发现了卷曲霉素潜在的新靶点，包括在DNA水平起作用的基因，如Rv0054（单链结合蛋白）和Rv3715c（重组酶RecR），以及参与细胞分裂的基因，如Rv3260c（whiB2）。此外，NADH脱氢酶基因簇和ATP合酶基因簇受到抑制。
