Foulkes Daniel M, Cooper Daniel M, Westland Catherine, Byrne Dominic P
Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool Liverpool L69 7ZB UK
RSC Chem Biol. 2025 Jun 19. doi: 10.1039/d5cb00016e.
In terms of biomass, bacteria are the most successful organisms on earth. This is partly attributed to their tremendous adaptive capabilities, which allows them to sense and rapidly organise responses to changing environmental stimuli. Using complex signalling mechanisms, bacteria can relay cellular information to fine-tune their metabolism, maintain homeostasis, and trigger virulence processes during infection. Across all life, protein phosphorylation represents the most abundant signalling mechanism, which is controlled by a versatile class of enzymes called protein kinases and their cognate phosphatases. For many years, histidine kinase (HK)-containing two-component systems (TCSs) were considered the canonical instruments of bacterial sensing. However, advances in metagenomics has since proven that bacterial phosphorelay is in fact orchestrated by a functionally diverse array of integrated protein kinase types, including Ser, Thr, Tyr and Arg-targeting enzymes. In this review, we provide an up-to-date appraisal of bacterial kinase signalling, with an emphasis on how these sensing pathways are regulated to modulate kinase output. Finally, we explore how selective kinase inhibitors may be exploited to control infections and combat the looming health emergency of multidrug resistant bacteria.
就生物量而言，细菌是地球上最成功的生物。这在一定程度上归因于它们巨大的适应能力，这种能力使它们能够感知并迅速组织对不断变化的环境刺激的反应。利用复杂的信号传导机制，细菌可以传递细胞信息，以微调其新陈代谢、维持体内平衡，并在感染期间触发毒力过程。在所有生命形式中，蛋白质磷酸化是最丰富的信号传导机制，它由一类多功能酶——蛋白激酶及其同源磷酸酶控制。多年来，含有组氨酸激酶（HK）的双组分系统（TCSs）被认为是细菌传感的经典工具。然而，宏基因组学的进展后来证明，细菌磷酸信号传递实际上是由一系列功能多样的整合蛋白激酶类型精心编排的，包括靶向丝氨酸、苏氨酸、酪氨酸和精氨酸的酶。在这篇综述中，我们对细菌激酶信号传导进行了最新评估，重点是这些传感途径如何被调节以调节激酶输出。最后，我们探讨了如何利用选择性激酶抑制剂来控制感染，并应对迫在眉睫的多重耐药细菌健康危机。
