Protein synthesis, antibacterial drug chloramphenicol

Figure 9.3 Targets for antibacterial drugs. The various classes of antibacterial drugs exert their effects at one of the four fundamental structural components of bacteria. Each of these components is vulnerable to drug attack. Penicillin, for example, attacks at the level of the cell wall chloramphenicol, however, works at the level of bacterial protein synthesis.

An interesting exception to the absolute validity of the tifth postulate is the considerable activity of chloramphenicol derivatives in cell-free model systems of protein synthesis when these derivatives are substituted with amino acyl residues instead of with dichloroacetyl as is the antibiotic itself (rev. in 2°)). This has been traced to the necessity of the dichloroacetyl grouping in aiding in the permeation of the antibiotic through the bacterial envelope 21 The amino acyl derivatives have very low antibacterial activity 20. Permeation failures of actinomycin D, macrolides and distamycin A with respect to certain families of bacteria occlude the action of these antibiotics on their intracellular drug receptors and target reactions but can be overcome experimentally by measures which render test organisms permeable. 

Antibacterial drugs that affect bacterial protein synthesis include the aminoglycosides, tetracyclines, macrolides, and the single drug chloramphenicol. 

Antibacterial drugs that inhibit protein synthesis aminoglycosides, tetracyclines, macrolldes and chloramphenicol... 

In contrast, the toxic agents cycloheximideemetine,amd puromycin, inhibit protein synthesis in animal cells as well as in protozoa and yeast. A rational design of antibacterial agents might well concentrate on drugs which act by the same mechanism as chloramphenicol. 

The ability of streptomycin, under certain conditions, to induce misreading of the genetic code and to produce nonsense polypeptides, may be phenomena of the laboratory unrelated to the clinical use of this drug (Luzzatto, Apirion, and Schlessinger, 1968). Streptomycin is lethal to cells only when they are vigorously engaged in protein synthesis. For this reason, some other inhibitors of protein synthesis, notably chloramphenicol and tetracycline, interfere with the antibacterial action of streptomycin. 

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