Filling holes in peptidoglycan biogenesis of Escherichia coli

Abstract

The peptidoglycan cell wall is an essential mesh-like structure in most bacteria. It is built outside the cytoplasmic membrane by polymerizing a disaccharide-pentapeptide into glycan chains that are crosslinked by peptides. The disaccharide-pentapeptide is synthetized as a lipid-linked precursor called lipid II, which is exported across the cytoplasmic membrane so that synthases can make new glycan chains. Growth of the peptidoglycan wall requires careful balancing of synthesis of glycan chains and hydrolysis of the preexisting structure to allow incorporation of new material. Recent studies in Escherichia coli have advanced our understanding of lipid II translocation across the membrane and how synthases are regulated to ensure proper envelope growth.

Figure 1. IM-localized steps in PG biogenesis in E. coli

Lipid II is synthesized in the cytoplasmic leaflet of the IM and translocated by a flippase. Then, the GT activity of bifunctional PBPs (blue) use lipid II to synthetize glycan chains, while its TP activity crosslinks the new chains to the preexisting matrix.

Figure 2. Regulation of PBP1a and PBP1b

A. LpoA stimulates TP activity of PBP1a, resulting in an increase in GT activity. B. LpoB stimulates GT activity of PBP1b, resulting in an increase in TP activity (black arrows). CpoB negatively regulates this activation of TP activity by LpoB. TolA can stop the effect of CpoB on the TP activity of PBP1b and activate its GT activity. Stimulatory and inhibitory effects are denoted with pointed and blunt arrows, respectively.