Inhibition of Cell Wall Synthesis

Proanthocyanidins Bacteria Ceii coat poiymers Inhibition of cell-associated proteolysis inhibition of cell wall synthesis [76]... 

Pharmacology Meropenem is a broad-spectrum carbapenem antibiotic. The bactericidal activity of meropenem results from the inhibition of cell-wall synthesis. Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. 

Pharmacology This product is a formulation of imipenem, a thienamycin antibiotic, and cilastatin sodium, the inhibitor of the renal dipeptidase, dehydropeptidase-1, which is responsible for the extensive metabolism of imipenem when it is administered alone. Cilastatin prevents the metabolism of imipenem, increasing urinary recovery and decreasing possible renal toxicity. The bactericidal activity of imipenem results from the inhibition of cell-wall synthesis, related to binding to penicillin-binding proteins (PBP). 

Mechanism of Action Inhibition of cell wall synthesis... 

C. Inhibition of Cell Wall Synthesis Remained Attractive—Cell Wall... 

In comparison with the penicillin and cephalosporin derivatives, the peptide antibiotics are not numbered among the major antibiotics . Their action mechanisms vary, e.g. inhibition of cell-wall synthesis, increased permeability of the cell wall, or influence on nucleic acid synthesis. 

Inhibitions of cell wall biosynthesis can be determined independently from DNA, RNA and protein biosyntheses. They will usually have been signaled by bactericidal effects and lysis of the test culture. In many instances, inhibition of cell wall synthesis results in the progressive accumulation of intermediates which can be assayed colorimetrically64, 6J) for N-acylaminohexose in acid-soluble fractions of the test bacteria. 

Inhibition of cell wall synthesis leads to bacterial cell lysis (bursting) and death. Agents operating in this way include penicillins and cephalosporins. Since animal cells do not have a cell wall, they are unaffected by such agents. 

An understanding of the biochemistry of peptidoglycan (PG murein) that comprises bacterial cell walls is very important medically since blockage of its synthesis was the first, and continues to be a primary, point of attack in the control of bacterial infection. In addition to inhibition of cell wall synthesis, antimicrobial drug s main mechanisms are interference with nucleic acid synthesis, inhibition of folate metabolism, and binding to ribosomes to disrupt protein synthesis (Table 16-2). 

Inactivation of certain enzyme systems involved in the oxidative metabolism of sensitive organisms by polymyxin and colistin has also been reported. This, however, might be a secondary effect . Bacitracin has been reported to interfere with cell wall synthesis. It causes Staphylococcus aureus to lyse , to form protoplasts and to accumulate cell wall precursors " . The incorporation of radioactive amino acids into cell wall mucopeptides is inhibited. Bacitracin has further been found to prevent Staphylococcus aureus from synthesizing /3-galactosidase , yet it does not interfere with the incorporation of radioactive lysine into cells . In experiments with Staphylococcus aureus, bacitracin and penicillin were shown to share a common binding site on the membrane , a result which could not be confirmed in similar experiments with B. megateriumP . Recently a direct effect of bacitracin on the cytoplasmic membrane has been demonstrated, and it was suggested that the inhibition of cell wall synthesis could be a secondary effect . ... 

These agents bind to penicillin binding proteins. Like penicillins, they must enter the cell wall through porins and attach to penicillin-binding proteins (PBPs). The binding of the drug to these proteins mediates an inhibition of cell wall synthesis and leads to autolysis. 

Novobiocin induces hlamentation in Gram-negative rods [10-13] with subsequent vacuolation [12] and loss of intracellular materials [14]. It is, however, debatable whether the induction of filamentous forms is characteristic of a particular biochemical effect. Some workers have advocated that filamentation indicates a specific inhibition of cell wall synthesis [15,1, but a number of antibacterial agents that exert their effects elsewhere in the cell also induce filamentation, for example mitomycin C [17], acridines [18, 19], nalidixic acid [20], ultraviolet light [21] and m-cresol [22]. It is probable, therefore, that filamentation induced by novobiocin is not wholly related to a specific effect of the antibiotic. 

Other investigations have shown that novobiocin causes a non-specific inhibition of cell wall synthesis in Staph, aureus and Strept. faecium [23, 31, 32] and that in E. coli the novobiocin-induced inhibition of cell wall synthesis is secondary to the inhibition of nucleic acid syntheses [33]. 

C3c4. Inhibition of cell wall synthesis (L) C3c5. Synthetic auxins (O)... 

Inhibition of cell wall synthesis The peptidoglycan layer is important for cell wall structural integrity, being the outermost and primary component of the wall. Inhibitors of cell wall synthesis act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls and thus come to degradation of the cell wall. 

The Relationship between Inhibition of Cell Wall Synthesis and Bacterial Lethality... 

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