Inclusion of pyrazinamide (PZA) in the tuberculosis (TB) drug regimen during the 1970s enabled a reduction in treatment duration from 12 to 6 months. PZA has this remarkable effect in patients despite displaying poor potency against Mycobacterium tuberculosis (Mtb) in vitro. The pharmacological basis for the in vivo sterilizing activity of the drug has remained obscure and its bacterial target controversial. Recently it was shown that PZA penetrates necrotic caseous TB lung lesions and kills nongrowing, drug-tolerant bacilli. Furthermore, it was uncovered that PZA inhibits bacterial Coenzyme A biosynthesis. It may block this pathway by triggering degradation of its target, aspartate decarboxylase. The elucidation of the pharmacological and molecular mechanisms of PZA provides the basis for the rational discovery of the next-generation PZA with improved in vitro potency while maintaining attractive pharmacological properties.

中文翻译：

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吡嗪酰胺杀菌活性背后的药理和分子机理。

在1970年代的结核病（TB）药物治疗方案中纳入吡嗪酰胺（PZA），可使治疗时间从12个月缩短至6个月。尽管PZA在体外对结核分枝杆菌（Mtb）的效能较弱，但在患者中仍具有显着效果。该药物的体内灭菌活性的药理基础仍然不清楚，其细菌靶标也引起争议。最近显示，PZA可穿透坏死的结核性TB肺部病变，并杀死不生长的，耐药菌。此外，发现PZA抑制细菌辅酶A的生物合成。它可能通过触发其目标天冬氨酸脱羧酶的降解来阻断该途径。