Team 1: Molecular interactions with the bacterial cell wall

Team Members

  • Francesca Mosca (PhD student)
  • Alicja Razew (postdoctoral researcher)

Presentation

Understanding the structural organization of the bacterial wall, and its spatial and temporal evolution as a function of its environment, remains a key element in understanding the molecular mechanisms taking place on the bacterial surface. Our previously published results have established that solid-state NMR, combined with solution NMR, is a technique of choice for the detailed study of the bacterial wall and the interactions between its various constituents. Spectra recorded on intact samples of isolated walls, or even whole bacteria, show that it is possible to obtain atomic-scale information on its organization or maturation, particularly under the influence of antibiotic treatments. Our work has shown that NMR is particularly useful for studying low-affinity and possibly transient interactions, such as those between antibiotics and target proteins (PBP, Ldt, β-lactamases), and for characterizing flexible, heterogeneous systems such as those found in bacterial wall components. These results have enabled us to extend our studies to lipopolyssacharides covering the bacterial cell surface and their interactions with their transport system through the wall.

In parallel with these developments, the team has successfully carried out a number of information-rich studies on systems strongly implicated in antibiotic resistance phenomena or potential targets for the development of new antibiotics: LpoP in Pseudomonas aeruginosa, MapZ in Streptococcus pneumoniae and PBP4 in Staphyloccocus aureus. Publications on the Lpo system describe the first PBP activators to be identified, enabling peptidoglycan growth to be coupled to elongation or cell division. This work provides a detailed understanding of the molecular mechanisms of activation of the proteins involved, a key step in analyzing the regulation of peptidoglycan synthesis during the cell cycle.

Ongoing Scientific Projects

  • ANR Project "OM-Pseudo" 2023-2030.
    "Outer membrane assembly controlled by peptidoglycan maturation in Pseudomonas"
  • Projet ITN BREAKthrough : 2023- 2026
    “Breaking the barrier - An integrated multidisciplinary approach to kill Gram-negative bacteria through existing antibiotics by making their outer membrane permeable”.

Recent Publications