Bacterial Response to Starvation
Modulating essential cellular processes in response to fluctuations in nutrient availability is a crucial process for all living cells. However, the underlying molecular mechanisms remain largely unknown, especially in bacteria. Recently, we uncovered the nitrogen-related phosphotransferase system (PTSNtr) as a first mechanism that regulates cell cycle progression upon nitrogen starvation in the a-proteobacterium Caulobacter crescentus. This mechanism allows cells to sense nitrogen – but not carbon – starvation by way of detecting glutamine deprivation, and to trigger accumulation of the alarmone (p)ppGpp. Accumulation of (p)ppGpp in C. crescentus increases the doubling time, the motility, the survival in stationary, the G1 lifetime and the tolerance to bactericidal antibiotics.
However, the mechanism(s) targeted by (p)ppGpp and responsible for all these effects remains unknown. In this proposal, we will first further characterize PTSNtr in C. crescentus, notably by checking whether the levels of (p)ppGpp and PTSNtr components oscillate throughout the cell cycle. Then we will combine genetic and biochemical approaches to find actors involved in the (p)ppGpp production upon carbon starvation. Finally, we will characterize the impact of the transcriptional reprogramming in the (p)ppGpp-dependent effects and determine the complete (p)ppGpp transcriptome. Indeed, our preliminary data strongly suggest that the RNA polymerase (RNAP) might constitute the major (p)ppGpp target in C. crescentus.
This research could lead to a better understanding of bacterial adaptation to stressful conditions and metabolic constraints, but also to promising perspectives to combat tolerance to bactericidal antibiotics, a phenomenon strongly influenced by (p)ppGpp.
Contact : Régis Hallez
