The increasing prevalence of multidrug-resistant pathogens necessitates the urgent development of new antimicrobial agents with innovative modes of action for the next generation of antimicrobial therapy. Bacterial transcription has been identified and widely studied as a viable target for antimicrobial development. The main focus of these studies has been the discovery of inhibitors that bind directly to the core enzyme of RNA polymerase (RNAP). Over the past two decades, substantial advancements have been made in understanding the properties of protein–protein interactions (PPIs) and gaining structural insights into bacterial RNAP and its associated factors. This has led to the crucial role of computational methods in aiding the identification of new PPI inhibitors to affect the RNAP function. In this context, bacterial transcriptional PPIs present promising, albeit challenging, targets for the creation of new antimicrobials. This review will succinctly outline the structural foundation of bacterial transcription networks and provide a summary of the known small molecules that target transcription PPIs.

中文翻译：

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抑制细菌 RNA 聚合酶功能和蛋白质-蛋白质相互作用：下一代抗菌治疗的一种有前途的方法

多重耐药病原体的日益流行需要迫切开发具有创新作用模式的新型抗菌药物，用于下一代抗菌治疗。细菌转录已被确定为抗菌药物开发的可行目标并得到广泛研究。这些研究的主要焦点是发现直接与 RNA 聚合酶 (RNAP) 核心酶结合的抑制剂。在过去的二十年中，人们在了解蛋白质-蛋白质相互作用 (PPI) 的特性以及获得细菌 RNAP 及其相关因素的结构见解方面取得了重大进展。这使得计算方法在帮助识别新的 PPI 抑制剂以影响 RNAP 功能方面发挥着至关重要的作用。在这种背景下，细菌转录质子泵抑制剂（PPI）为新型抗菌药物的研发提供了充满希望但充满挑战的目标。这篇综述将简要概述细菌转录网络的结构基础，并总结已知的靶向转录 PPI 的小分子。