Infection and Immunity
It has recently become evident that the bacterial stringent response is regulated by a triphosphate alarmone (pGpp) as well as the canonical tetra- and pentaphosphate alarmones ppGpp and pppGpp [together, (p)ppGpp]. Often dismissed in the past as an artifact or degradation product, pGpp has been confirmed as a deliberate endpoint of multiple synthetic pathways utilizing GMP, (p)ppGpp, or GDP/GTP as precursors. Some early studies concluded that pGpp functionally mimics (p)ppGpp and that its biological role is to make alarmone metabolism less dependent on the guanine energy charge of the cell by allowing GMP-dependent synthesis to continue when GDP/GTP has been depleted. However, recent reports that pGpp binds unique potential protein receptors and is the only alarmone synthesized by the intestinal pathogen Clostridioides difficile indicate that pGpp is more than a stand-in for the longer alarmones and plays a distinct biological role beyond its functional overlap (p)ppGpp.
© 2023 Malik et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0).
Original Publication Citation
Malik, A., Hept, M. A., & Purcell, E. B. (2023). Sound the (smaller) alarm: The triphosphate magic spot nucleotide pGpp. Infection and Immunity, 91(4), 1-12, Article e00432-22. https://doi.org/10.1128/iai.00432-22
Malik, Areej; Hept, Megan A.; and Purcell, Erin B., "Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp" (2023). Chemistry & Biochemistry Faculty Publications. 245.