Section: New Results

Models of carbon metabolism in bacteria

Adaptation of bacterial growth to changes in environmental conditions, such as the availability of specific carbon sources, is triggered at the molecular level by the reorganization of metabolism and gene expression: the concentration of metabolites is adjusted, as well as the concentration and activities of enzymes, the rate of metabolic reactions, the transcription and translation rates, and the stability of proteins and RNAs. This reprogramming of the bacterial cell is carried out by i) specific interactions involving regulatory proteins or RNAs that specifically respond to the change of environmental conditions and ii) global regulation involving changes in the concentration of RNA polymerase, ribosomes, and metabolite pools that globally affect the rates of transcription, translation, and degradation of all RNAs and proteins. While these phenomena have been well studied in steady-state growth conditions, much less is known about adaptation during growth transitions. In particular, only very few data are available on changes in the concentration and activity of the transcription and translation machineries and almost no data exost for the dynamic response of the degradation machinery.

In the framework of the PhD thesis of Manon Morin, supported by a Contrat Jeune Scientifique INRA-Inria (2012-2015), the collaboration of Delphine Ropers with Muriel Cocaign-Bousquet and Brice Enjalbert at INRA/INSA de Toulouse has allowed to disentangle the role of post-transcriptional regulation from other regulatory interactions in the dynamic adaptation of central carbon metabolism in E. coli. In a multi-scale analysis of a wild-type strain and its isogenic mutant attenuated for the protein CsrA, a variety of experimental data have been acquired in relevant conditions, including growth parameters, gene expression levels, metabolite pools, enzyme activities and metabolic fluxes. Data integration, metabolic flux analysis and regulation analysis revealed the pivotal role of post-transcriptional regulation for shaping carbon metabolism. In particular, the work has shed light on csrA essentiality and has provided an explanation for the glucose-phosphate stress observed in the mutant strain. A paper summarizing the work has been published in Molecular Microbiology this year [14]. A follow-up study conducted with various mutant strains of the carbon storage regulator system has elucidated the role of post-transcriptional regulation in the dynamics of glycogen storage and consumption, as well as the key role of the latter compound for bacterial fitness. A paper summarizing the work is being prepared for publication.

The collaboration with INRA/INSA de Toulouse is continued in the context of the PhD thesis of Thibault Etienne, funded by an INRA-Inria PhD grant, with the objective of developing models able to explain how cells coordinate their physiology and the functioning of the transcription, translation, and degradation machineries following changes in the availability of carbon sources in the environment.