While the cell wall must be rigid enough to maintain high intracellular pressures and withstand environmental assaults, it also needs to be flexible enough to allow for cellular expansion. In the case of mycobacteria, layers of polysaccharides and long-chain lipids are added to the PG layer, making the cell wall structure even more complex ( Jankute et al., 2015). In addition, the PG mesh can be decorated with secondary cell wall polymers, such as wall teichoic acids (polyol-phosphate polymers) or capsule polysaccharides that are covalently attached to PG ( Rajagopal and Walker, 2017).

The assembly process can be further subdivided into polymerization of the GlcNAc-MurNAc-pentapeptide via glycosyltransferase reactions catalyzed by class A PBPs and SEDS proteins, and crosslinking of the peptide sidestems into a tight meshwork by class A and B PBPs and L,D-transpeptidases in a not (yet) fully-understood manner ( Zhao et al., 2017). Synthesis steps include cytoplasmic generation of the lipid-linked disaccharide-pentapeptide precursor lipid II, translocation of lipid II to the outside of the cell by flippases (MurJ and/or Amj) and finally assembly of the cell wall by penicillin-binding proteins (PBPs) and Shape, Elongation, Division, and Sporulation (SEDS) proteins ( Ruiz, 2008 Typas et al., 2011 Meeske et al., 2015, 2016 Cho et al., 2016 Taguchi et al., 2019). PG is synthesized on the external face of the cytoplasm. The cell wall consists mainly of peptidoglycan (PG), a mesh of polysaccharide strands (composed of a poly- backbone) cross-linked via short peptide bridges attached to the MurNAc residues ( Vollmer et al., 2008a). In addition, bacterial cell wall fragments can have immunostimulatory and cytotoxic properties and thus play important roles in pathogenesis and disease ( Goldman et al., 1982 Fleming et al., 1986 Royet et al., 2011 Sorbara and Philpott, 2011 Jutras et al., 2019).

Historically, the cell wall has been of intense research interest due to its necessity for most bacteria and absence from the eukaryotic realm, positioning it as an ideal target for some of our most powerful antibiotics ( Schneider and Sahl, 2010). The bacterial cell wall is a complex, mesh-like structure that in most bacteria is essential for maintenance of cell shape and structural integrity.

Cell wall of gram negative bacteria