Make and Break the Alarmone: regulation of (p)ppGpp Synthetase/Hydrolase Enzymes in Bacteria

Séverin Ronneau, Régis Hallez

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Bacteria use dedicated mechanisms to respond adequately to fluctuating environments and to optimize their chances of survival in harsh conditions. One of the major stress responses used by virtually all bacteria relies on the sharp accumulation of an alarmone, the guanosine penta- or tetra-phosphate commonly referred to as (p)ppGpp. Under stressful conditions, essentially nutrient starvation, these second messengers completely reshape the metabolism and physiology by coordinately modulating growth, transcription, translation and cell cycle. As a central regulator of bacterial stress response, the alarmone is also involved in biofilm formation, virulence, antibiotics tolerance and resistance in many pathogenic bacteria. Intracellular concentrations of (p)ppGpp are determined by a highly conserved and widely distributed family of proteins called RelA-SpoT Homologs (RSH). Recently, several studies uncovering mechanisms that regulate RSH activities have renewed a strong interest in this field. In this review, we outline the diversity of the RSH protein family as well as the molecular devices used by bacteria to integrate and transform environmental cues into intracellular (p)ppGpp levels.

Original languageEnglish
Article numberfuz009
Pages (from-to)389-400
Number of pages12
JournalFEMS microbiology reviews
Issue number4
Publication statusPublished - 1 Jul 2019


  • (p)ppGpp
  • RSH
  • Rel
  • SpoT
  • alarmone
  • second messenger
  • Hydrolases/genetics
  • Virulence/genetics
  • Ligases/genetics
  • Bacterial Proteins/genetics
  • Stress, Physiological/genetics
  • Bacteria/enzymology
  • Gene Expression Regulation, Bacterial


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