To survive to fluctuating environments, bacteria have evolved complex regulatory pathways that sense and respond adequately to changing conditions. One of these systems used by literally all bacteria is based on the alarmone (p)ppGpp. This second messenger accumulates upon starvation to essential elements (carbon, nitrogen, phosphorus, …), and the burst of (p)ppGpp modulates several cellular processes (transcription, metabolism, growth, cell cycle, virulence, …). By combining genetic and biochemical approaches in the bacterial models Caulobacter crescentus and Escherichia coli, we are (i) characterizing mechanisms that trigger (p)ppGpp accumulation in response to nutritional stresses, and (ii) looking for direct (p)ppGpp targets.
The dimorphic life cycle of C. crescentus is the result of an obligate asymmetric cell division that gives rise to a larger stalked cell and a smaller swarmer cell. The swarmer progeny is specialized for dispersal whereas the stalked cell helps in colonizing favorable substrates. Caulobacter uses metabolic checkpoints to modulate cell cycle and development depending on nutrient availability. We investigate the molecular basis of these metabolic checkpoints, in particular those used to coordinate metabolism with cell division, as well as their implication in cell size homeostasis.
During the C. crescentus cell cycle a single round of chromosome replication (S phase) culminates in an asymmetric cell division (G2) that produces a motile swarmer cell and a sessile stalked cell. Whereas the stalked cell is able to immediately re-initiate a new round of replication and cell division, the swarmer cell remains in a motile, replication inert phase (G1) before differentiating into a replication-competent stalked cell. Exit from G1 is controlled by environmental factors like nutrient availability, but also by regulatory systems. We study the molecular mechanisms determining the time spent in G1 phase as well as the factors triggering the G1-to-S transition.
Brucella abortus is an intracellular pathogen that shares several common features with C. crescentus such as an asymmetric cell division and regulatory pathways controlling cell cycle and differentiation. Moreover the cell cycle is tightly controlled during infection of host cells (X. De Bolle lab) and metabolism plays a crucial role in Brucella virulence (J-J. Letesson lab). Our studies on B. abortus aim at understanding how metabolism and cell cycle are coordinated during intracellular invasion.