Takayama K, Wang L, David H L
Antimicrob Agents Chemother. 1972 Jul;2(1):29-35. doi: 10.1128/AAC.2.1.29.
When an actively growing culture of the H37Ra strain of Mycobacterium tuberculosis was exposed to isoniazid at a concentration of 0.5 mug/ml, the cells began to lose their ability to synthesize mycolic acids immediately. After 60 min, the cells had completely lost this ability. The synthesis of the three mycolate components-alpha-mycolate, methoxymycolate, and beta-mycolate-was inhibited. The viability of the isoniazid-treated cells was unaffected up to about 60 min of exposure, after which time there was a gradual decline in the viability to about 18% after 180 min. Correspondingly, growth of the drug-treated cells slowed down and stopped after 24 hr. The inhibition of the synthesis of mycolic acids was reversible if the drug was removed before the loss of viability set in. Incubation of the viable cells in the absence of the drug for 24 hr restored the mycolate synthesis. These results strongly suggest that the inhibition of the synthesis of the mycolic acids is closely associated with the primary mechanism of action of isoniazid on the tubercle bacilli. The sequence of events which leads to the loss of viability of cells exposed to isoniazid is described.
当将结核分枝杆菌H37Ra菌株的活跃生长培养物暴露于浓度为0.5微克/毫升的异烟肼时,细胞立即开始丧失合成分枝菌酸的能力。60分钟后,细胞完全丧失了这种能力。三种分枝菌酸成分——α-分枝菌酸、甲氧基分枝菌酸和β-分枝菌酸的合成均受到抑制。在暴露约60分钟之前,经异烟肼处理的细胞活力未受影响,此后活力逐渐下降,180分钟后降至约18%。相应地,药物处理的细胞生长在24小时后减慢并停止。如果在细胞活力丧失之前去除药物,分枝菌酸合成的抑制是可逆的。将存活细胞在无药物的情况下培养24小时可恢复分枝菌酸的合成。这些结果强烈表明,分枝菌酸合成的抑制与异烟肼对结核杆菌的主要作用机制密切相关。描述了导致暴露于异烟肼的细胞丧失活力的一系列事件。