ABSTRACT

Introduction .................................................................................................................................... 159 Gram-Positive and Gram-Negative Bacteria ................................................................................. 160 Dimensions of the Peptidoglycan................................................................................................... 161 Chemical Structure of Murein ....................................................................................................... 163 Peptidoglycan Biosynthesis ............................................................................................................ 166 Three-Dimensional Structure of PG .............................................................................................. 171 Cell Wall as a Dynamic Structure ................................................................................................. 172 Cell Wall Biosynthesis Enzymes as Targets for Antibiotics .......................................................... 176 Peptidoglycan Integrity as a Response Stimulus ........................................................................... 177 Conclusion ...................................................................................................................................... 178 References ...................................................................................................................................... 178

The bacterial cell wall is a heteropolymer that is a structural component of the cell envelope of most bacteria, with the exception of the Mycoplasma and a small group of highly specialized prokaryotes.94, 95, 119, 154, 162, 177 Although often used interchangeably, the terms “cell wall” and “cell envelope” are distinct. The cell envelope is the multilayer barrier that separates and protects the cytoplasm of the bacterium from its external environment. The cell envelope includes the peptidoglycan cell wall, the membrane(s), the periplasmic space, and the macromolecules that are associated with these structures. The integrity of the cell wall is necessary for bacterial viability. The cell wall heteropolymer is biosynthesized from both amino acid and saccharide precursors, and in nal form consists of a three-dimensional array of glycan strands interconnected by peptide cross-links. In recognition of the presence of peptide cross-linking of the glycan strands, the term “peptidoglycan” is often used as a synonym for the cell wall, particularly where emphasis of the molecular basis for the cell wall structure is appropriate. The term “murein” is a synonym of peptidoglycan. Exhaustive hydrolysis of the murein, by glycosylases (such as lysozyme) and by cell wall peptidases, degrades the cell wall into its constituent muropeptides. The core structure of the intact muropeptide is a glycan strand. The structure of this glycan, that of a repeating [N-acetylglucosamine]-[N-acetylmuramic] (abbreviated as NAG-NAM) disaccharide, is highly conserved among the Gram-negative and Gram-positive bacteria. The structure of the peptide cross-links is, however, much more variable. In the Gram-positive and Gram-negative eubacteria, the cell wall is a single polymeric molecule that surrounds the entire bacterium. The term describing this single polymeric molecule is “sacculus.” The sacculus of the Gram-negative bacterium is found in the periplasm, a space between the inner membrane and outer membrane. In the Gram-positive bacterium, the cell wall forms the exterior surface of the bacterium and overlays an inner (periplasm-like) space located above the single cell (plasma) membrane.