Only PBP1 (class B PBP with only TP activity, bPBP) and PBP2 (class A bifunctional PBP with both TG and TP activities, aPBP) are essential and sufficient for septal and peripheral PG synthesis in S. The major human pathogen Staphylococcus aureus has a minimalist PBP system, as it encodes only four PBPs, PBP1 to PBP4 ( 8). Since the cell wall is essential for maintaining bacterial life, PBPs and PG synthesis are a target of some of the most important antibiotics, β-lactams (penicillins) and glycopeptides (vancomycin) ( 6, 7). The final stages of assembly of this large polymeric molecule are mediated by penicillin-binding proteins (PBPs), key PG synthases that, through their transglycosylase (TG) and transpeptidase (TP) activities, polymerize glycan chains and cross-link them into a mesh-like hydrogel ( 4, 5). Peptidoglycan (PG) is the major structural component of the bacterial cell wall and is essential for maintaining cell shape, integrity, and survival ( 1 – 3).
Together, these results lead to a model for septal PG synthesis where PBP1 enzyme activity is required for the characteristic architecture of the septum and PBP1 protein molecules enable the formation of the septal plate. The transpeptidase activity of PBP1 is also essential, but its loss leads to a strikingly different phenotype of thickened and aberrant septa, which is phenocopied by the morphological effects of adding the PBP1-specific β-lactam, meropenem. The PASTA domains can bind PG and thereby potentially coordinate the cell division process.
Loss of PBP1, or just its C-terminal PASTA domains, results in cessation of division at the point of septal plate formation. aureus, and here, we demonstrate that it has multiple essential functions associated with its enzymatic activity and as a regulator of division. Penicillin-binding proteins (PBPs) are essential for the final steps of PG biosynthesis their transpeptidase activity links the peptide side chains of nascent glycan strands. Peptidoglycan (PG) is the major structural component of the septum, and our recent studies in the human pathogen Staphylococcus aureus have revealed a complex, multistage PG architecture that develops during septation. Bacterial cell division is a complex process requiring the coordination of multiple components to allow the appropriate spatial and temporal control of septum formation and cell scission.
0 kommentar(er)
