Evidence for a dual role of PBP1 in the cell division and cell separation of Staphylococcus aureus

Abstract

SummaryPenicillin-binding proteins (PBPs) catalyse the synthesis of cell wall peptidoglycan. PBP1 of Staphylococcus aureus is a high-molecular-weight monofunctional transpeptidase (TPase) and previous studies with a conditional mutant showed that this protein was essential for bacterial growth and survival: cells in which PBP1 was depleted stopped dividing but continued to enlarge in size, accompanied by rapid loss of viability. Also, cell walls produced under PBP1 depletion appeared to have normal composition. We describe here construction of a second PBP1 mutant in which the active site of the TPase domain was inactivated. Cells in which the wild-type PBP1 was replaced by the mutant protein were able to initiate and complete septa and undergo at least one or two cell divisions after which growth stopped accompanied by inhibition of cell separation, downregulation in the transcription of the autolytic system and production of cell walls with increased proportion of monomeric and dimeric muropeptides and decrease in oligomeric muropeptides. PBP1 seems to perform a dual role in the cell cycle of S. aureus: as a protein required for septation and also as a transpeptidase that generates a critical signal for cell separation at the end of cell division.

β-Lactams Interfering with PBP1 Induce Panton-Valentine Leukocidin Expression by Triggering sarA and rot Global Regulators of Staphylococcus aureus

“…We tested this hypothesis by altering PBP1 function with an inducible PBP1-specific antisense RNA and observed a dose-dependent relationship between the pbp1 antisense RNA level and the luk-PV mRNA level, thus confirming that PBP1 depletion may lead to enhanced PVL expression by S. aureus. Recent reports from Pereira et al (50,51) underlined the major role of PBP1 in the formation of the division septum and the separation of daughter cells at the end of cell division, probably in conjunction with the autolytic system. In E. coli, beta-lactam inactivation of PBP3, an orthologue of S. aureus PBP1 also involved in peptidoglycan synthesis during cell division, induced the SOS-promoting recA and lexA genes (44).…”

Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus

“…PBP1 is a monofunctional transpeptidase, essential for cell viability and required for septation and cell separation at the end of cell division (37). It localizes to the division septum through a mechanism that is independent of its ability to bind its substrate (38). PBP2 is an essential bifunctional transglycosylase and transpeptidase that plays a central role in the ability of bacteria to express their resistance to antibiotics (39) and localizes to the division septum in a way that is dependent on its ability to recognize the translocated substrate (32).…”

The Staphylococcus aureus Chaperone PrsA Is a New Auxiliary Factor of Oxacillin Resistance Affecting Penicillin-Binding Protein 2A

“…They participate in the late stages of PG biosynthesis catalyzing the transglycosylation and/or transpeptidation of precursors into the growing PG. The four native staphylococcal PBPs have been functionally and structurally scrutinized over the past 40 years (30)(31)(32)(33)(34)(35). MRSA strains possess an exogenous PBP with very low affinity for ␤-lactam antibiotics, namely, PBP2A.…”