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Penicillin-binding protein 1 (PBP1) of Staphylococcus aureus has multiple essential functions in cell division

DOI: 10.1128/mbio.00669-22 DOI Help

Authors: Katarzyna Wacnik (University of Sheffield) , Vincenzo A. Rao (Newcastle University) , Xinyue Chen (University of Sheffield) , Lucia Lafage (University of Sheffield) , Manuel Pazos (Newcastle University) , Simon Booth (Newcastle University) , Waldemar Vollmer (Newcastle University) , Jamie K. Hobbs (University of Sheffield) , Richard J. Lewis (Newcastle University) , Simon J. Foster (University of Sheffield)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Mbio

State: Published (Approved)
Published: June 2022
Diamond Proposal Number(s): 18598

Open Access Open Access

Abstract: 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, multistage PG architecture that develops during septation. 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. 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 β-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.

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 20/06/2022 11:33


Discipline Tags:

Antibiotic Resistance Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)