Decoding the regulation of (p)ppGpp, a universal alarmone controlling cell cycle progression in Caulobacter crescentus

Promoter

Dr. Régis HALLEZ, UNamur, Research Unit in Biology of Microorganisms (URBM)

Jury

Régis Hallez (Supervisor), Jean-Yves Matroule (President), Jan MICHIELS (Jury), Urs Jenal (Jury) & Abel Garcia-Pino (Jury)

Summary

To survive and proliferate, every living organism is subjected to fundamental needs, such as finding nutrients in its environment. From bacteria to humans, nutrients provide energy and building blocks required for cell growth and proliferation. Nevertheless, nutrients availability is changing in most environments. To face these changes, organisms use complex signal transduction networks to develop sophisticated strategies that ensure their survival. The alarmone (p)ppGpp is commonly used by bacteria to quickly respond to nutrient starvation. Although (p)ppGpp synthetases such as SpoT have been extensively studied, little is known about the molecular mechanisms stimulating alarmone synthesis upon starvation. This research work describe an essential role of the nitrogen-related phosphotransferase system (PTSNtr) in controlling (p)ppGpp accumulation in Caulobacter crescentus. We show that cells sense nitrogen starvation by way of detecting glutamine deprivation using the first enzyme of PTSNtr, EINtr. Decreasing intracellular glutamine concentration triggers phosphorylation of EINtr and its downstream components HPr and EIIANtr. Once phosphorylated, both HPr~P and EIIANtr~P stimulate (p)ppGpp accumulation by modulating SpoT activities. This burst of second messenger primarily impacts the non-replicative phase of the cell cycle by extending the G1 lifetime. This work highlights a new role for bacterial PTS systems in stimulating (p)ppGpp accumulation in response to metabolic cues and in controlling cell cycle progression and cell growth.