Régis VILLET

Identify the array of efflux pumps of Staphylococcus aureus that contribute to multiple antimicrobial resistance in vivo, to elucidate the factors that determine their expression, their role in microbial physiology, and their effect on bacterial response to antimicrobial infection.

Identify the contribution of antibiotics and DNA repair pathways on emergence of bacterial resistance in Staphylococcus aureus.

Peptidoglycan, the essential component of the bacterial cell wall, consists of glycan chains cross-linked by short peptides. Many species of Gram-positive bacteria produce branched peptidoglycan precursors, carrying highly diverse side chains, assembled by the aminoacyl transferases of the Fem Family. These enzymes, which have the particularity to use an aminoacyl-tRNA as the substrate, are potential targets for the development of new antibiotics active against multi-resistant bacteria since the production of branched precursors is essential for expression of beta-lactam resistance.
I characterized the interactions of Fem transferases with their two substrates for rational design of inhibitors of these enzymes.