Kilburn J O, Takayama K
Antimicrob Agents Chemother. 1981 Sep;20(3):401-4. doi: 10.1128/AAC.20.3.401.
We examined the early effects of ethambutol on the synthesis of trehalose monomycolate, trehalose dimycolate, and free mycolic acid in actively growing cells of Mycobacterium smegmatis. At about 1 min after the addition of 3.0 micrograms of ethambutol per ml, the cellular level of trehalose monomycolate began to increase over the control culture. This was followed 8 to 12 min later by the cellular increases in free mycolic acid and trehalose dimycolate over the control culture and the inhibition of incorporation of mycolic acid into the cell wall. Exposure of M. smegmatis to ethambutol for more than 30 min caused all of these lipids to leak out of the cells more rapidly than in the control cells. The mechanism by which ethambutol initiates these events is unknown, but these early imbalances in lipid synthesis may be responsible for the lethal action of this drug.
我们研究了乙胺丁醇对耻垢分枝杆菌活跃生长细胞中海藻糖单霉菌酸酯、海藻糖双霉菌酸酯和游离霉菌酸合成的早期影响。在每毫升添加3.0微克乙胺丁醇后约1分钟,海藻糖单霉菌酸酯的细胞水平开始高于对照培养物。8至12分钟后,游离霉菌酸和海藻糖双霉菌酸酯的细胞水平高于对照培养物,并且霉菌酸掺入细胞壁受到抑制。耻垢分枝杆菌暴露于乙胺丁醇超过30分钟导致所有这些脂质比对照细胞更快地从细胞中泄漏出来。乙胺丁醇引发这些事件的机制尚不清楚,但脂质合成中的这些早期失衡可能是该药物致死作用的原因。