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目的:探讨bostrycin的抗结核菌活性及其对细菌基因表达的影响。方法:利用纸片扩散法初步鉴定海洋微生物代谢产物的抗结核菌活性。针对有潜在抗结核活性的化合物用绝对浓度间接法测定该化合物抗结核菌的最低抑菌浓度。应用结核cDNA芯片检测化合物处理组与对照组的基因表达谱的变化。结果:初步鉴定发现bostrycin在卡介苗平板上有明显抑菌圈,绝对浓度间接法测定显示醌类化合物bostrycin对卡介苗、结核分枝杆菌H37Rv、结核分枝杆菌临床分离株(包括敏感株和耐药株)均有抑制作用,尤其对耐多药结核分支杆菌有较好抗菌效果。结核cDNA芯片检测提示,在检测的3 875条结核分枝杆菌基因中,bostrycin处理组与对照组比较,有44条差异表达基因,其中18条上调,26条下调;这些差异表达的基因功能涉及核苷酸、脂类、能量、辅酶、碳水化合物的代谢,DNA复制、转录、翻译、氨基酸转运和代谢,细胞膜合成等。结论:本研究为抗结核新药的开发和新的抗结核菌作用靶点的研究提供了有价值的实验基础。
Objective: To investigate the anti-TB activity of bostrycin and its effect on bacterial gene expression. Methods: The antimicrobial activity of marine microbial metabolites was identified by disk diffusion method. For compounds with potential antitubercular activity, the minimum inhibitory concentrations of the compounds against M. tuberculosis were determined by the absolute concentration indirect method. The changes of gene expression profile of compound treated group and control group were detected by using cDNA microarray. Results: Preliminary identification showed that bostrycin showed obvious inhibition zone on BCG plate. Indirect determination of absolute concentration of bostrycin showed that the activity of bostrycin against BCG, Mycobacterium tuberculosis H37Rv and clinical isolates of M. tuberculosis (including sensitive and resistant strains ) Are inhibited, especially for multi-drug resistant Mycobacterium tuberculosis has good antibacterial effect. The results of tuberculosis cDNA microarray indicated that there were 44 differentially expressed genes among the 3875 M. tuberculosis genes detected in bostrycin group, of which 18 were up-regulated and 26 were down-regulated. These differentially expressed genes involved Nucleotides, lipids, energy, coenzymes, carbohydrate metabolism, DNA replication, transcription, translation, amino acid transport and metabolism, cell membrane synthesis and the like. Conclusion: This study provides a valuable experimental basis for the development of new anti-TB drugs and new targets of anti-TB activity.