Antibacterial agents cell-wall synthesis inhibition

To be an effective antibacterial agent, a drng mnst inhibit an enzyme that is present in the bacteria bnt not in the host. One well-known example is a transpeptidase involved in cell wall synthesis in some bacteria. Inhibition prevents bacteria from synthesising their cell wall so that proliferation stops. A drng that inhibits this enzyme is the antibiotic, penicillin first nsed in 1941 (see Chapter 17). However, the first dnrg to inhibit bacterial growth was developed from a dye (Box 3.8). 

Antibacterial agents which inhibit cell wall synthesis... 

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. 

Cephalosporin An antibacterial agent that inhibits cell wall synthesis. 

Mechanism of Action An antibacterial UTI agent that inhibits the synthesis of bacterial DNA, RNA, proteins, and cell walls by altering or inactivating ribosomal proteins. Therapeutic Effect Bacteriostatic (bactericidal at high concentrations). Pharmacokinetics Microcrystalline form rapidly and completely absorbed macrocrystalline form more slowly absorbed. Food increases absorption. Protein binding 40%. Primarily concentrated in urine and kidneys. Metabolized in most body tissues. Primarily excreted in urine. Removed by hemodialysis. Half-life 20-60 min. 

Antibacterial agents may be classified as bacteriostatic or bactericidal (Table 51-3). For agents that are primarily bacteriostatic, inhibitory drug concentrations are much lower than bactericidal drug concentrations. In general, cell wall-active agents are bactericidal, and drugs that inhibit protein synthesis are bacteriostatic. 

Early workers [29] found that, like benzylpenicillin, vancomycin, ristocetin and bacitracin, novobiocin caused an excessive accumulation of cell wall precursor, uridine diphosphate-7V-acetylmuramic acid-L-alanine-D-glutamic acid-L-lysine-D-alanine-D-alanine (UDP-MurNAc-L-ala-D-glu-L-lys-D-ala-D-ala) in Staph, aureus and it was thus considered that novobiocin was a specific inhibitor of peptidoglycan synthesis with an effect similar to that of penicillin. However, subsequent studies led to the withdrawal of this hypothesis [26], since novobiocin caused the accumulation of other precursor-type compounds and also strongly inhibited both nucleic acid and protein synthesis in this organism. Thus, accumulation of particular precursors does not necessarily reflect the site of action of an antibacterial agent [30]. 

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