Exploring the structure of the Enterococcal Polysaccharide Antigen to understand its role in cell division, antimicrobial resistance, and surface reco

This project focuses on the structure/function analysis of a surface polysaccharide produced by enterococci, required for normal cell growth, division, resistance to antibiotics and pathogenesis. This enterococcal polysaccharide antigen (EPA) is encoded by two gene clusters: (i) 18 genes extremely conserved encoding a core synthetic machinery and (ii) a set of genes variable between strains, responsible for the decoration of the polysaccharide backbone.

We have built a mutant with a complete deletion of the epa variable region and shown that the decoration of EPA (but not its core structure) is essential for the biological activity of this polymer. We propose to investigate EPA structural properties and dissect the contribution EPA decoration to bacterial physiology and antibiotic resistance and recognition by bacteriophages.

We will take a multidisciplinary approach to explore EPA structure and to understand how EPA controls the distribution and activity of surface proteins involved in cell wall assembly and resistance to antibiotics. The project will involve state-of-the-art methodologies including super-resolution microscopy (fluorescence and electron microscopy), structural glycobiology (NMR, mass spectrometry) and conventional approaches to study bacterial physiology and antimicrobial resistance.

The candidate will work with members of the supervisors' laboratories studying bacterial cell surface assembly, host-pathogen interaction, and bacteriophages.