What Genomics Has Taught Us about Bacterial Cell Wall Biosynthesis

Abstract

This chapter focuses only on the major structural polysaccharide components of bacterial cell walls, so to present a coherent commentary on the impact of genomics on the understanding of cell wall biosynthesis. The chapter is organized to relate a commentary on the basic processes of cell wall biosynthesis derived from decades of chemical analyses and classical genetics studies in the pregenomic era. Recently, researchers have made tremendous progress in imaging of bacterial cell walls by cryoelectron microscopy and atomic force microscopy, which has provided new detailed insights into cell wall organization in both gram-positive and gram-negative bacteria. The construction of the murein sacculus is essentially a two-stage process. In the first, a disaccharide-peptide monomer unit is assembled by using UDP-linked and then polyprenyl phosphate-linked intermediates. Next, transglycosylases (TGs) catalyze the polymerization of the glycan chains and transpeptidases (TPs); the penicillin-binding proteins (PBPs) cross-link the peptide cross-bridges between glycan chains and thus incorporate nascent material into the existing PG sacculus framework. An architecturally similar but less complex cell wall core structure is conserved across the Corynebacterineae, which presented the possibility that comparative genomics might scout new routes toward the understanding of the construction of these fascinating structures. In this era of rapidly emerging multidrug resistance, the efforts to understand bacterial pathogens through study of their cell wall biosynthesis, in identification of novel targets, by defining modes of action of current drugs, and by investigating the development of resistance, must keep pace with the rapidly evolving adversaries.