Peptidoglycan assembly machines: The Staphylococcus aureus Penicillin-Binding Proteins

Dissertation presented to obtain the Ph.D degree in Biology

The bacterial cell wall (CW) is of critical importance to cell viability. Impairment of CW synthesis or integrity rapidly leads to cell lysis and death. As there is no equivalent structure to the bacterial CW in mammalian cells, many important antibiotics target the enzymes responsible for its synthesis. The scaffold of the CW consists of the polymer peptidoglycan (PGN), a meshlike structure composed of glycan strands cross‐linked by short peptides. The final steps of PGN synthesis are catalysed by the penicillin‐binding proteins (PBPs), which assemble lipid‐linked disaccharide peptide precursors of PGN into high molecular weight oligomers via transglycosylation and transpeptidation reactions. These proteins have been proposed to work in multi‐enzyme complexes that would also include CW hydrolases.(...)