PhyGeBaC / Deutscher
PROJECT DE RECHERCHE / THEMATIQUE
The availability of carbon sources is an essential requirement for efficient growth of all living organisms. Bacteria have developed complex regulatory systems in order to optimize the use of carbon sources. In most cases, the genes encoding the enzymes for the uptake and metabolism of a specific carbon source are only expressed when the substrate is present in the medium (substrate induction). Our research group is mainly studying carbohydrate transport via the PEP:glycose phosphotransferase system (PTS), which also catalyzes the phosphorylation of the sugar during its transport. We are presently working on the glucose, cellobiose and arabitol PTS uptake systems of Listeria monocytogenes, on ribitol transport in Lactobacillus casei and on maltose and maltose oligosaccharide utilization in Enterococcus faeclis. Components of the PTS were also found to exert numerous regulatory functions in carbon, nitrogen and phosphate metabolism and to affect the virulence of certain pathogens. Carbon catabolite repression and inducer exclusion are well-studied examples. The regulatory functions of the PTS are mediated either by direct phosphorylation of the target protein or by phosphoylation-dependent protein/protein interaction, mainly with transcription regulators.
The mechanisms of carbon catabolite repression assure that, when more than one carbon source is available, the one which can be most efficiently metabolized will be preferentially used. Several mechanisms controlling carbon catabolite repression either at the transcription level or at the carbohydrate transport step (inducer exclusion) have evolved. We presently study inducer exclusion and CcpA-independent transcription regulation of the mannitol operon in B. subtilis and L. casei and the regulation of sporulation-related functions in Bacillus cereus. We are specifically interested in the control of the expression of the genes encoding the mannose/glucose, arabitol and cellobiose uptake systems in L. monocytogenes and the repressive effects exerted by the metabolism of these saccharides on the expression of the virulence genes of this pathogen.
In addition, in numerous other pathogens carbon metabolism was found to directly control the expression of virulence genes or to affect other virulence-related processes. We try to unravel the correlation between carbon metabolism and virulence in Neisseria meningitidis, Escherichia coli (ExPEC), Brucella melitensis and Enterococcus faecalis. In Neisseria meningitidis components of an incomplete PTS control the activity of a repressor regulating the expression of pili and capsule genes, whereas in Brucella melitensis the same proteins control the expression of the virB genes, a type IV secretion system essential for the virulence of this organism.
All these regulatory mechanisms are based on sensing the phosphorylation state of a PTS protein. Elevated phosphorylation of PTS proteins can favour a phosphoryl group transfer to a non PTS protein thus changing the activity of an enzyme or a transcription regulator. Alternatively, elevated or diminished phosphorylation of PTS proteins can favour the formation of protein/protein, protein/DNA or protein/RNA complexes. Our group intensively studies protein phosphorylation at all different levels (ATP- and PEP-dependent protein phosphorylation at Ser, Thr, Tyr as well as Cys and His residues). We are also analyzing the phospho-proteome of L. monocytogenes in order to identify protein phosphorylation-dependent signalling pathways involved in the virulence of this organism. We could recently demonstrate that one of the virulence proteins is indeed phosphorylated at several amino acids.
We collaborate with the research groups of M.K. Taha and Pascale Cossart (Inst. Pasteur, Paris); Philippe Gilot (University of Tours); Didier Lereclus (INRA, MICALIS Jouy en Josas); Herman van Tilbeurgh (University Paris Sud, Orsay); Céline Henri (INRA, Jouy en Josas), Marie-Françoise Noirot-Gros (INRA, Jouy en Josas), Axel Hartke (University of Caen), Jörg Stülke (University of Göttingen, Germany), Maria Jesus Yebra and Vicente Monedero (IATA-CSIC, Valencia, Spain), Milton H. Saier (University of California at San Diego, USA), John Thompson (NIH, Bethesda, USA), Christian Magni (University of Rosario, Argentina).
Institut Micalis (UMR1319/INRA-AgroParisTech and SNC9130/CNRS)
Rédaction : Micalis
Date de création : 14 Avril 2011
Mise à jour : 12 Février 2014