

However, each set of enzymes remains active upon inhibition of the respective other one and aPBPs and Rod-complex components show different sub-cellular motion ( Cho et al., 2016). In the past, aPBPs have been suggested to work in close association with the MreB-based Rod complex ( Pazos et al., 2017), motivated by biochemical interactions between PBP1a and the Rod-complex TPase PBP2 ( Banzhaf et al., 2012), and by similar interactions between PBP1b and the divisome TPase PBP3 ( Bertsche et al., 2006). aPBPs also interact with cell-wall cleaving lytic transglycosylases and DD-endopeptidases ( Banzhaf et al., 2020), consistent with the possibility that they form multi-enzyme complexes responsible for both cell-wall expansion and insertion. Mutants in either PBP1a-LpoA or PBP1b-LpoB are viable and don’t show any strong phenotype during regular growth, but mutants in components from both pairs are synthetically lethal ( Yousif et al., 1985 Typas et al., 2010 Paradis-Bleau et al., 2010).

PBP1a and PBP1b are activated by the outer-membrane lipoprotein cofactors LpoA and LpoB, respectively ( Typas et al., 2010 Paradis-Bleau et al., 2010 Typas et al., 2012).

Second, bi-functional and essential class-A PBPs (aPBP’s) PBP1a and PBP1b carry out both TPase and TGase activities. Together with the MreB cytoskeleton these and other Rod-complex components persistently rotate around the cell ( van Teeffelen et al., 2011 Dominguez-Escobar et al., 2011 Garner et al., 2011 Cho et al., 2016 Morgenstein et al., 2017) and are responsible for rod-like cell shape. First, the Rod complex comprises the Penicillin-Binding Protein PBP2, an essential TPase, and RodA, an essential TGase from the SEDS (shape, elongation, division and sporulation) family of proteins ( Meeske et al., 2016 Emami et al., 2017). During side-wall elongation, these two activities are carried out by two sets of machinery ( Cho et al., 2016). To avoid the formation of large pores in the cell wall during growth, cell-wall insertion and cell-wall cleavage must be tightly coordinated ( Vollmer et al., 2008).Ĭell-wall insertion involves two kinds of enzymatic reactions: transglycosylase (TGase) activity to extend the glycan strands, and transpeptidase (TPase) activity to create cross-links between glycan strands. coli the cell wall is a thin two-dimensional polymer that consists of mostly parallel glycan strands oriented circumferentially around the cell axis ( Gan et al., 2008) and peptide cross-links that connect adjacent glycan strands.

The peptidoglycan cell wall is responsible for both cell shape and mechanical integrity of the bacterial cell envelope ( Typas et al., 2010 Vollmer and Bertsche, 2008).
