Textbook - BIOLOGICAL CHEMISTRY - Hubsky Yu.I. - 2000

Chapter I. BIOMOLECULES AND CELL STRUCTURES

CHAPTER 4. CARBOHYDRATES AND THEIR DERIVATIVES

4.4. PEPTIDOGLYCANS OF THE MICROBIAL CELL WALL

Most microbes spend a significant portion of their life cycle as unicellular organisms; therefore, their fragile cytoplasmic membrane is encased in an outer Cell wall that protects the membrane from damaging environmental factors.

The basis of the Introduction/37.html">Bacterial cell wall is formed by special Heteropolysaccharides linked to Membrane Proteins in the form of Proteoglycans or peptidoglycans.

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Muramin is a bacterial cell wall heteropolysaccharide whose unbranched chains consist of N-acetylglucosamine and N-acetylmuramic acid residues linked together by a β-1,4-glycosidic bond. Muramic acid is a derivative of D-glucosamine with a lactic acid (lactyl) residue attached at the 3rd position.

The Structural Organization of muramin is similar to that of Cellulose and Chitin (unbranched chains with β-bonds between monomers), which determines the mechanical strength of these heteropolysaccharides and their Structural and functional role. Furthermore, the human gastrointestinal tract lacks Enzymes capable of breaking down these Polysaccharides.

Fig. 4.2. Schematic representation of the Molecular organization of the bacterial cell wall peptidoglycan — using murein from Salmonella aureus as an example (after A. Lehninger, 1974). A. Structure of cross-peptide linkages between individual polysaccharide chains (X denotes an N-acetylglucosamine residue; Y denotes an N-acetylmuramic acid residue). Tetrapeptide (L-Ala - D-Gln - L-Lys - D-Ala) side chains of each polysaccharide (muramic) chain are interconnected by pentapeptide "bridges" consisting of five Glycine residues. B. Parallel heteropolysaccharide chains of murein are linked together into a unified macromolecular peptidoglycan framework via cross-peptide chains.

Murein. The formation of the bacterial cell wall involves muramin linked to peptide chains in the form of a proteoglycan (or peptidoglycan) known as murein. Murein is a mixed biopolymer consisting of parallel polysaccharide chains cross-linked by short peptide chains. Essentially, muramin can be visualized as a single molecule that envelops the bacterial cell like a giant sac or scaffold.

Gram-Positive and Gram-Negative Microorganisms

In addition to the peptidoglycan network described above, bacterial Cell walls contain various auxiliary BIOCHEMICAL COMPONENTS OF polysaccharide, lipid, and protein nature, which vary among different microorganisms.

The compositional features of cell walls provide the molecular basis for the classical Classification of Bacteria into gram-positive and gram-negative, which differ in their staining behavior when treated with a mixture of crystal violet (gentian violet), iodine, and safranin. When sequentially treated with these Reagents, gram-positive bacteria retain the iodine-crystal violet complex and stain blue-violet, whereas gram-negative bacteria do not yield a positive reaction to this stain.

Gram-positive microorganisms are bacteria whose cell wall biochemical profile is characterized by the presence of Teichoic Acids embedded within the peptidoglycan matrix. Teichoic acids are complex polymers whose chains are built from glycerol and ribitol alcohol residues linked by phosphodiester bonds. In some teichoic acids, D-Alanine and D-glucose or N-acetyl-D-glucosamine residues are attached to the main molecular backbone. Peptidoglycans constitute the major portion (40–90%) of The Cell wall mass in gram-positive bacteria.

Gram-negative microorganisms are bacteria whose cell walls feature an additional outer membrane. The outer membrane consists of a layer of lipopolysaccharides, Lipids, and proteins, beneath which lies a layer of peptidoglycans that, in turn, cover the inner (cytoplasmic) membrane. The total peptidoglycan content in the cell walls of gram-negative bacteria is significantly lower (5–10%) than that of gram-positive organisms.

Antibiotics as Cell Wall Synthesis Inhibitors

The Cleavage or disruption of the synthesis of individual components within the microbial cell wall peptidoglycan structure forms the molecular basis for the antibacterial Action of Certain antibiotics.

Penicillins are antibiotics produced by mold Fungi of the genus Penicillium, exhibiting significant bactericidal activity against gram-positive microorganisms. The biochemical MECHANISM OF ACTION of penicillins involves the inhibition of a final stage in peptidoglycan formation—specifically, the interaction between pentaglycine and the terminal D-alanine of the side tetrapeptide chains linked to the heteropolysaccharide. This antibiotic action disrupts the Formation of the murein cell wall scaffold, ultimately leading to bacterial cell death.

Cephalosporins—antibiotics isolated from the fungus Cephalosporium acremonium—act similarly to penicillins. Cephalosporins also suppress The activity of enzymes essential for the formation of bacterial cell wall peptidoglycans.

Lysozyme is an antibacterial factor of animal origin that serves as a component of non-specific host resistance. By mechanism of action, lysozyme Functions as a muramidase. It is a hydrolytic enzyme that cleaves (1→4)-glycosidic bonds between disaccharide components in the muramin polysaccharide chain, leading to the destruction of the microbial cell wall.