The team investigates the metabolism of peptidoglycan, which is the main constituent of the bacterial cell wall. This exoskeleton is essential for cell integrity, division and morphogenesis. It is the target of a large number of antibacterial agents, including antibiotics, with a wide variety of structures and mechanisms of action. Our project aims to better understand underexplored membrane steps in peptidoglycan biosynthesis and to study/design new molecules capable of interfering with these steps for therapeutic purposes.
Structure of peptidoglycan from Escherichia Coli
Peptidoglycan is composed of long glycan chains, which are cross-linked via short peptide stems. Its disaccharide-peptide subunit is polymerized on the outer side of the membrane by the conjugated action of glycosyltransferases and transpeptidases enzymes. The subunit is first assembled on the undecaprenyl phosphate (C55-P) carrier lipid from two nucleotide precursors, UDP-GlcNAc and UDP-MurNAc-peptide. The membrane intermediate thus formed, lipid II, is translocated across the membrane to allow the transfer of the subunit to the peptidoglycan polymer in elongation. The lipid carrier is released as undecaprenyl pyrophosphate (C55-PP), which is recycled. Finally, the peptidoglycan undergoes a series of species-specific maturation and decoration reactions that may confer resistance to antimicrobial agents or allow bacteria to escape recognition by the host immune system.