Abstract
Peptidoglycan (PG) is an essential component of the bacterial cell wall that maintains the shape and integrity of the cell. The PG precursor lipid II is assembled at the inner leaflet of the cytoplasmic membrane, translocated to the periplasmic side, and polymerized to glycan chains by membrane anchored PG synthases, such as the class A Penicillin-binding proteins (PBPs). Polymerization of PG releases the diphosphate form of the carrier lipid, undecaprenyl pyrophosphate (C55-PP), which is converted to the monophosphate form by membrane-embedded pyrophosphatases, generating C55-P for a new round of PG precursor synthesis. Here we report that deletion of the C55-PP pyrophosphatase gene pgpB in E. coli increases the susceptibility to cefsulodin, a β-lactam specific for PBP1A, indicating that the cellular function of PBP1B is impaired in the absence of PgpB. Purified PBP1B interacted with PgpB and another C55-PP pyrophosphatase, BacA and both, PgpB and BacA stimulated the glycosyltransferase activity of PBP1B. C55-PP was found to be a potent inhibitor of PBP1B. Our data suggest that the stimulation of PBP1B by PgpB is due to the faster removal and processing of C55-PP, and that PBP1B interacts with C55-PP phosphatases during PG synthesis to couple PG polymerization with the recycling of the carrier lipid and prevent product inhibition by C55-PP.
Highlights
Peptidoglycan (PG) is an essential component of the bacterial cell envelope protecting the cells from bursting due to its turgor and maintaining the shape of the cell
Polymerization of PG releases the diphosphate form of the carrier lipid, undecaprenyl pyrophosphate (C55-PP), which is converted to the monophosphate form by membrane-embedded pyrophosphatases, generating C55-P for a new round of PG precursor synthesis
We report that deletion of the C55-PP pyrophosphatase gene pgpB in E. coli increases the susceptibility to cefsulodin, a β-lactam specific for PBP1A, indicating that the cellular function of PBP1B is impaired in the absence of PgpB
Summary
Peptidoglycan (PG) is an essential component of the bacterial cell envelope protecting the cells from bursting due to its turgor and maintaining the shape of the cell. The two final PG precursors contain a carrier lipid, undecaprenyl phosphate (C55-P) and are assembled at the inner leaflet of the cytoplasmic membrane. The transferase MraY produces lipid I from the soluble nucleoside-precursors UDP-MurNAc-pentapeptide and the carrier lipid, C55-P (Barreteau et al, 2008). MurG catalyses the transfer of a GlcNAc moiety from UDP-GlcNAc to lipid I, forming lipid II (Liu & Breukink, 2016). Lipid II is translocated across the cytoplasmic membrane by proteins belonging to the SEDS (shape, elongation, division and sporulation) family, MurJ or both, and polymerized by PG glycosyltransferases (GTases) (Ruiz, 2015, Leclercq et al, 2017, Mohammadi et al, 2011)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
