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

Posted on 10.06.2022 - 11:57 by Katarzyna Wacnik

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. Peptidoglycan (PG) is the major structural component of the septum, and our recent studies in the human pathogen Staphylococcus aureus have revealed a complex, multi-stage PG architecture that develops during septation. Penicillin binding proteins (PBPs) are essential for the final steps of PG biosynthesis – their transpeptidase activity links together the peptide sidechain of nascent glycan strands. PBP1 is required for cell division in S. aureus and here we demonstrate that it has multiple essential functions associated with its enzymatic activity and as a regulator of division. Loss of PBP1, or just its C-terminal PASTA domains, results in cessation of division at the point of septal plate formation. The PASTA domains can bind PG and thereby potentially coordinate the cell division process. 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 b-lactam, meropenem. 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.

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Wacnik, Katarzyna; Rao, Vincenzo; Chen, Xinyue; Lafage, Lucia; Pazos, Manuel; Booth, Simon; et al. (2022): Penicillin-Binding Protein 1 (PBP1) of Staphylococcus aureus Has Multiple Essential Functions in Cell Division. The University of Sheffield. Collection. https://doi.org/10.15131/shef.data.c.5656339.v1
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FUNDING

MICA: Mechanistic understanding of cell wall biosynthesis to combat antimicrobial resistance

Medical Research Council

SHeffield IMAging (SHIMA)

Medical Research Council

The Physics of Antimicrobial Resistance

Engineering and Physical Sciences Research Council

The bacterial cell wall in life and death

Wellcome Trust

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