Défense de thèse de doctorat en sciences biologiques : "regulation of (p)ppGpp", par Séverin Ronneau

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

Jury

Jan MICHIELS (KULeuven), Urs JENAL (University of Basel), Abel GARCIA-PINO (ULB), Jean-Yves MATROULE, président (UNamur), Régis HALLEZ, promoteur (UNamur)

Résumé

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 (PTS^Ntr) 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 PTS^Ntr, EI^Ntr. Decreasing intracellular glutamine concentration triggers phosphorylation of EI^Ntr and its downstream components HPr and EIIA^Ntr. Once phosphorylated, both HPr~P and EIIA^Ntr~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.

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