PhyGeBaC / Deutscher
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Physiologie et Génétique des Bactéries
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RESEARCH PROJECT
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).
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 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, fructose and cellobiose uptake systems in L. monocytogenes and the regulatory 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 affect the expression of virulence genes or to influence other virulence-related processes. We try to unravel the correlation between carbon metabolism and virulence in Neisseria meningitidis, Escherichia coli (ExPEC) and Brucella melitensis. In N. meningitidis components of a sugar uptake system 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.
Most of these regulatory networks imply protein phosphorylation steps. Their effects are transmitted either by changing directly the activity of an enzyme or by affecting protein/protein, protein/DNA or protein/RNA interactions. Our group therefore 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 collaborate with the 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); Jean-Jacques Letesson and Xavier De Bolle (University of Namur); Jörg Stülke (University of Göttingen); Milton H. Saier, University of San Diego.
Our research activities are mainly funded by the Agence Nationale de la Recherche (ANR). Our group contains personnel employed by the INRA and the CNRS.
Writing:
Micalis
Creation date: 14 April 2011
Update: 15 September 2011
