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Home > Departments > Microbiology > Thierry TOUZÉ : Bacterial Cell Envelopes and Antibiotics

Thierry TOUZÉ : Group Presentation

Project

Our laboratory develops detailed investigations of the metabolism and structure of peptidoglycan, one of the main components of the bacterial cell wall. This complex cell-sized polymer that is essential and specific of the bacterial world is formed of long glycan chains cross-linked by short peptides.




It determines the characteristic cell shape (spherical or rod), is implicated in cell growth and cell division processes, and serves as a platform for the binding of various other cell envelope components (proteins, polysaccharides). Its main role is to maintain the cell integrity by protecting bacteria against the internal osmotic pressure. Degrading the peptidoglycan structure or inhibiting its biosynthesis results in bacterial cell lysis. Detailed investigations of this pathway therefore present a double interest, fundamental and applied, all the enzymes involved in this process constituting potential targets that could be exploited for a search of new antibiotics.




Some steps of this pathway still remain to be elucidated or are only partially characterized. This is particularly true for membrane steps, the nature of the proteins implicated (in most cases integral membrane proteins) and the difficulty to overexpress and purify them having clearly hampered the progress of our knowledge in that field. Therefore, significant efforts of our team were focused on these steps in recent years.

Our main projects concern:

  • (I) a global analysis of the variations of the peptidoglycan structure and of its metabolism encountered in bacterial world;
  • (II) the development of a general structure-activity relationships analysis within the family of Mur ligases which catalyze the formation of the peptide moiety of this polymer;
  • (III) the biochemical and structural characterization of membrane enzymes involved in the synthesis of peptidoglycan lipid intermediates I and II;
  • (IV) the elucidation of the metabolism of the carrier lipid undecaprenyl-phosphate which is required for the synthesis of this and various other cell envelope components;
  • (V) the exploitation of all these enzymes as potential targets for antibiotics;
  • (VI) the identification and characterization of bacteriocins targeting peptidoglycan metabolism;
  • (VII) the elucidation of the mode of action of antibiotics and the analysis of resistance mechanisms developed by bacteria;
  • (VIII) the identification of molecular determinants allowing the recognition of peptidoglycan by host innate immunity mechanisms during bacterial infection.

These projects are developed by using multidisciplinary approaches combining bacteriology, molecular biology, cellular biology, biochemistry, biophysics and chemistry. All this activity is performed thanks to numerous collaborations with academic and industrial partners which were developed within the frame of different national and international contracts (FP6 EUR-INTAFAR 2005-2010; PICS-CNRS; Proteus and Tournesol PHC; ANR Bactoprenyl 2012-2015; ANR MimictRNA 2013-2017; IAP iProS 2012-2017; FRM 2017-2019).

Keywords

Bacterial cell wall, peptidoglycan, metabolism, regulation, enzyme, membrane protein, inhibitor, antibiotic, bacteriocin, innate immunity.

Contact


TOUZE Thierry [Lecturer - UPSaclay]
Bacterial Enveloppes and Antibiotics [Leader]
01 69 82 61 25 Orsay - Bât 430

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