EXPLORING PEPTIDOGLYCAN RECOGNITION AND SUBCELLULAR TARGETING OF THE UBIQUITOUS PEPTIDOGLYCAN BINDING DOMAIN LYSM

Bacterial surface proteins play a critical role in fundamental processes such as cell growth, division, and environmental interactions. In pathogens, these proteins are essential for tissue invasion and evading the host immune system. Core to all these functions is the ability to bind to the bacterial cell wall, and thus be appropriately displayed for interaction with the environment. This project will focus on a protein domain called LysM (for Lysin Motif) found in all bacterial species. LysM mediates non-covalent attachment of proteins to peptidoglycan (PG), the essential component of the bacterial cell envelope which is the target of the most important antibiotic ever discovered, penicillin
LysM domains are found in bacteria, plants, animals, and viruses, are absent in Archaea. These domains typically consist of one to twelve motifs, each about 45 amino acids long, with a conserved βααβ fold. Enzymes linked to LysM are used by bacteria to remodel the cell wall, build and destroy septa, and in pathogenesis. While the LysM fold is conserved, the amino acid sequences vary, and how these variations affect binding affinity or specificity is unknown. It has been shown that LysM motifs fold independently, allowing for additive binding strength without cooperative folding. In this project we will focus on two key enzymes in Enterococcus faecalis, AtlA and AtlB, that contain LysM domains and contribute to PG remodeling during growth. AtlA is mainly responsible for septum cleavage during cell division, while AtlB aids in overall PG turnover.
The major challenge lies in understanding the diversity of LysM domains. This research aims to explore how cell wall composition and LysM domain properties influence this targeting. Given the threat posed by E. faecalis as a drug-resistant pathogen, the findings could provide groundbreaking insights into bacterial cell wall interactions and lead to innovative strategies for combating antibiotic-resistant infections.

Supervisor

Dr Florence Vincent, AFMB , Aix-Marseille University, ED658 - Sciences du Vivant

Co-Supervisor

Dr Stéphane Mesnage, School of Bioscience, University of Sheffield, Microbiology

Intersectoral partner

CytobodX, France

International partner

School of Bioscience , University of Sheffield, United Kingdom

If you are interested please go to the website 

https://schadoc.univ-amu.fr/en/call-candidates/call-candidates/health-well-being/peplys

and at the bottom of the page there is the "APPLY" button that will take you the application interface.

The Architecture et Fonction des Macromolécules Biologiques (AFMB) laboratory is a center of structural biology localized on the Luminy campus in the South of Marseilles, France. It is overseen by the CNRS and AMU (UMR 7257) and in partnership with INRAe (USC AFMB 1408) and Inserm (U1324 ELR).

The aim of our researches is to depict the architecture of proteins or macromolecular assemblies at the molecular level to understand the biological mechanisms which they govern. The description of interactions between macromolecules or a macromolecule and a ligand is also crucial to manipulate these complex molecules. Finally, to understand the molecular diversity of members of some protein families, we also analyze the big data issued from large-scale genome sequencing centers.

The candiate should have skills in structural biology, biophysics and microbiology

The eligibilty criteria are on the Shadoc AMU website folling the link to apply for the project

https://schadoc.univ-amu.fr/en/call-candidates/call-candidates/health-well-being/peplys