The stringent response and physiological roles of (pp)pGpp in bacteria

In this Review, Corrigan and colleagues explore the broad range of metabolic pathways that guanosine pentaphosphate, guanosine tetraphosphate and guanosine 5 '-monophosphate 3 '-diphosphate regulate in the bacterial cell and emphasize the importance of these alarmones in regulating diverse metabolic processes. Moreover, they examine the contribution of these alarmones to virulence and chronic infection. 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.

Automated summary

This Review delves into the diverse metabolic pathways regulated in bacterial cells and emphasizes the importance of alarmones in the stringent response and bacterial pathogenesis. It highlights the complexity and broad range of functions controlled by these alarmones, providing an update on the enzymes involved in their turnover and discussing their role in virulence and chronic infection.