The stringent response is a stress signalling system mediated by the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) in response to nutrient deprivation. Recent research highlights the complexity and broad range of functions that these alarmones control. This Review provides an update on our current understanding of the enzymes involved in ppGpp, pppGpp and guanosine 5′-monophosphate 3′-diphosphate (pGpp) (collectively (pp)pGpp) turnover, including those shown to produce pGpp and its analogue (pp)pApp. We describe the well-known interactions with RNA polymerase as well as a broader range of cellular target pathways controlled by (pp)pGpp, including DNA replication, transcription, nucleotide synthesis, ribosome biogenesis and function, as well as lipid metabolism. Finally, we review the role of ppGpp and pppGpp in bacterial pathogenesis, providing examples of how these nucleotides are involved in regulating many aspects of virulence and chronic infection.

严格反应是一种应激信号系统，由四磷酸鸟苷 (ppGpp) 和五磷酸鸟苷 (pppGpp) 警报器介导，以响应营养缺乏。最近的研究突出了这些警报控制的复杂性和广泛的功能。本综述更新了我们目前对参与 ppGpp、pppGpp 和鸟苷 5'-单磷酸 3'-二磷酸 (pGpp)（统称为 (pp)pGpp）转换的酶的理解，包括那些显示产生 pGpp 及其类似物 (pp )pApp。我们描述了众所周知的与 RNA 聚合酶的相互作用以及由 (pp)pGpp 控制的更广泛的细胞靶标途径，包括 DNA 复制、转录、核苷酸合成、核糖体生物发生和功能，以及脂质代谢。最后，