Penicillin-Binding Protein 1 (PBP1) of Staphylococcus aureus Has Multiple Essential Functions in Cell Division

Bacterial cell wall peptidoglycan is essential, and its synthesis is the target of clinically important antibiotics such as β-lactams. β-lactams target penicillin-binding proteins (PBPs) that assemble new peptidoglycan from its building blocks. The human pathogen Staphylococcus aureus only has two essential PBPs that can carry out all the functions necessary for growth and division. In the absence of the confounding antibiotic resistance-associated PBP PBP2A, PBP1 is required for cell division, and here, we have found that it has several essential functions, both as an enzyme and as a coordinator by binding to cell division proteins and to its peptidoglycan product, via its PASTA domains. This has led to a new model for cell division with PBP1 responsible for the synthesis of the characteristic architectural features of the septum.