Tetracyclines selective toxicity

Although all tetracyclines have a similar mechanism of action, they have different chemical structures and are produced by different species of Streptomyces. In addition, structural analogues of these compounds have been synthesized to improve pharmacokinetic properties and antimicrobial activity. While several biological processes in the bacterial cells are modified by the tetracyclines, their primary mode of action is inhibition of protein synthesis. Tetracyclines bind to the SOS ribosome and thereby prevent the binding of aminoacyl transfer RNA (tRNA) to the A site (acceptor site) on the 50S ri-bosomal unit. The tetracyclines affect both eukaryotic and prokaryotic cells but are selectively toxic for bacteria, because they readily penetrate microbial membranes and accumulate in the cytoplasm through an energy-dependent tetracycline transport system that is absent from mammalian cells. 

Selective toxicity of these protein synthesis inhibitors against microorganisms may be explained by target differences. Chloramphenicol does not bind to the SOS ribosomal RNA of mammalian cells, though it can inhibit the functions of mitochotidrial ribosomes, which contain 70S ribosomal RNA. Tetracyclines have little effect on mammalian protein synthesis because an active efflux mechanism prevents their intracellular accumulation. 

Penicillins, cephalosporins, tetracyclines, acrinomvdns These are examples of classes of antibiotics each from a microorganism producing c) otoxic agents. The first three classes are selectively c) otoxic to bacteria, and the fourth cytotoxic to mammalian cancer cells, unfortunately with poor selective toxicity. The penicillins and cephalosporins inhibit bacterial cell wall synthesis, and tetracyclines selectively block protein synthesis at the bacterial ribosome. The actinomycins intercalate in a relative nonselective manner the... 

Which of the following explains why tetracycline is selective for prokaryotes and minimally toxic to humans ... 

Halling-Sprensen B., G. Sengelpv, and J. Tjpmelund (2002). Toxicity of tetracyclines and tetracycline degradation products to environmentally relevant bacteria, including selected tetracycline-resistant bacteria. Archives of Environmental Contamination and Toxicology 42 263-271. 

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