结核分枝杆菌异烟肼耐药性的分子遗传和生物化学机理

Molecular genetics and biochemical mechanisms for isoniazid resistance of Mycobacterium tuberculosis

枝菌酸是结核分枝杆菌细胞壁组分之一。异烟肼作用的主要靶标是参与枝菌酸生物合成的蛋白质。临床分离耐药株多数在KatG蛋白发生点突变,该蛋白也是INH作用靶标之一。但是,现有数据还不能解释INH耐药和INH杀灭细菌的全部机理。我们研究结核分枝杆菌耐药机理应该高起点,综合利用生物信息学、基因芯片、蛋白质组学、结构生物学等技术进行研究。

Mycolic acid is one of the essential components of the Mycobacterium tuberculosis cell wall. The primary target of INH is the proteins involved in the biosynthesis of the mycolic acids. Most clinical isolates have point mutation in KatG protein, which is also the target of INH. However, current available data can not fully explain the resistance of bacteria and how INH kill the bacteria. Studies should be carried out by integrating the bioinformatics, DNA chip, proteomics and structural biology.