SUMMARYPyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. Defining the mode of action for PZA will open new avenues for rational design of novel therapeutic approaches for the treatment of TB. In this review, we discuss the four prevailing models for PZA action, recent developments in modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.

中文翻译：

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吡嗪酰胺的令人困惑的抗结核作用。

概述吡嗪酰胺（PZA）是专门用于治疗结核病（TB）的基石抗菌药物。由于PZA能够将药物治疗缩短3个月并降低疾病复发率，因此被认为是药物易感性结核病的标准一线短期治疗和耐多药结核病的二线治疗方案的不可替代的组成部分。尽管对PZA及其在当前和将来的TB治疗方案中的关键作用进行了60多年的研究，但这种独特药物的作用方式仍不清楚。定义PZA的作用方式将为合理设计结核病治疗新方法开辟新途径。在这篇综述中，我们讨论了PZA作用的四种主要模型，PZA敏感性和耐药性调节的最新进展，