Archive | 2019
Peptidoglycan Structure, Biosynthesis, and Dynamics During Bacterial Growth
Abstract
The peptidoglycan is the key structural component of the bacterial cell wall that rests outside the cytoplasmic membrane and provides bacterial cells with physical strength and shape. It constitutes a huge mesh-like macromolecule composed of linear glycans held together by short peptides: the glycans consist of alternating amino sugars, N-acetylglucosamine (GlcNAc), and N-acetylmuramic acid (MurNAc), connected by β-1,4-glycosidic linkages, and the peptides include noncanonical d-amino acids and cross-link the glycan chains via binding to MurNAc. The peptidoglycan macromolecule is ubiquitous in bacteria, regardless of whether displaying a Gram-positive, Gram-negative, or complex mycobacterial cell envelope structure, and it is also highly restricted to bacteria, thereby distinguishing bacteria from eukaryotic microorganisms and archaea. In all bacteria, the peptidoglycan is synthesized from a lipid-anchored precursor that is preformed in the cytoplasm, flipped outward through the plasma membrane by channeling proteins (flippases), and is finally polymerized by membrane-bound, outward-facing synthetic enzymes (glycosyltransferases and transpeptidases) building a net-shaped covering of the entire bacterial cell, called the peptidoglycan sacculus. The peptidoglycan sacculus allows bacteria to cope with osmotic and environmental challenges, and it secures cell integrity during all stages of bacterial growth. It has to be sufficiently strong and rigid but, at the same time, flexible and dynamic to assure integrity of the cell during enlargement, division, and differentiation processes. Thus, the synthesis and integrity of the peptidoglycan are major targets of antibacterial therapeutics. We are summarizing in this chapter present knowledge including recent discoveries of peptidoglycan structure, assembly, and dynamics during bacterial growth.