tailieunhanh - Chapter 127. Treatment and Prophylaxis of Bacterial Infections (Part 2)

Inhibition of Cell-Wall Synthesis One major difference between bacterial and mammalian cells is the presence in bacteria of a rigid wall external to the cell membrane. The wall protects bacterial cells from osmotic rupture, which would result from the cell's usual marked hyperosmolarity (by up to 20 atm) relative to the host environment. The structure conferring cell-wall rigidity and resistance to osmotic lysis in both gram-positive and gram-negative bacteria is peptidoglycan, a large, covalently linked sacculus that surrounds the bacterium. In gram-positive bacteria, peptidoglycan is the only layered structure external to the cell membrane and is thick (20–80 nm); in. | Chapter 127. Treatment and Prophylaxis of Bacterial Infections Part 2 Inhibition of Cell-Wall Synthesis One major difference between bacterial and mammalian cells is the presence in bacteria of a rigid wall external to the cell membrane. The wall protects bacterial cells from osmotic rupture which would result from the cell s usual marked hyperosmolarity by up to 20 atm relative to the host environment. The structure conferring cell-wall rigidity and resistance to osmotic lysis in both gram-positive and gram-negative bacteria is peptidoglycan a large covalently linked sacculus that surrounds the bacterium. In gram-positive bacteria peptidoglycan is the only layered structure external to the cell membrane and is thick 20-80 nm in gram-negative bacteria there is an outer membrane external to a very thin 1-nm peptidoglycan layer. Chemotherapeutic agents directed at any stage of the synthesis export assembly or cross-linking of peptidoglycan lead to inhibition of bacterial cell growth and in most cases to cell death. Peptidoglycan is composed of 1 a backbone of two alternating sugars N-acetylglucosamine and N-acetylmuramic acid 2 a chain of four amino acids that extends down from the backbone stem peptides and 3 a peptide bridge that cross-links the peptide chains. Peptidoglycan is formed by the addition of subunits a sugar with its five attached amino acids that are assembled in the cytoplasm and transported through the cytoplasmic membrane to the cell surface. Subsequent cross-linking is driven by cleavage of the terminal stem-peptide amino acid. Virtually all the antibiotics that inhibit bacterial cell-wall synthesis are bactericidal. That is they eventually result in the cell s death due to osmotic lysis. However much of the loss of cell-wall integrity following treatment with cell wall-active agents is due to the bacteria s own cell-wall remodeling enzymes autolysins that cleave peptidoglycan bonds in the normal course of cell growth. In the presence of .