Thesis defense: Théodore Arnaud

Théodore Arnaud will present his research work that has been performed at CERMAV and ILL under the direction of Anne Imberty and Matthew Blakeley.

Antibiotic resistance is a growing global health threat, making the discovery of novel antibacterial therapeutics increasingly urgent. One promising strategy is to target the earliest stage of infection: bacterial recognition of and adhesion to host cell surfaces. Many pathogens achieve these steps by producing lectins, sugar-binding proteins that specifically recognize carbohydrate motifs found on glycoproteins, glycolipids of the host cell.

This project focuses on LecA, a lectin produced by Pseudomonas aeruginosa, a bacterium listed as a priority pathogen by the World Health Organization due to emergence of multi-antibiotic-resistant strains. LecA plays a key role in the early stages of infection and in biofilm formation, a major contributor to bacterial persistence and antibiotic resistance. LecA specifically binds the sugar moiety of globotriaosylceramide (Gb3), a glycolipid expressed on the surface of pulmonary epithelial cells, which exposes the trisaccharide epitope Gal(α1-4)Gal(β1-4)Glc.

The aim of this thesis is to characterize the interaction between LecA and Gb3 epitopes using neutron macromolecular crystallography (NMX), a structural biology technique that enables the visualization of hydrogen atoms through its isotope deuterium. This interdisciplinary work combines chemistry and biotechnology (production of deuterated carbohydrates by chemical synthesis and metabolic engineering of E. coli), biochemistry (protein production and purification), and biophysics (neutron and X-ray macromolecular crystallography, and affinity assays).