Translation and Antibiotics

Antibiotics are drugs that kill microorganisms. To make an effective antibiotic—not just any poison will do—the trick is to kill the microbe without harming the patient. Antibiotics must be carefully chosen so that they destroy bacterial cells but not the eukaryotic cells of their host.

Translation is frequently the target of antibiotics because translation is essential to all living organisms and differs significantly between bacterial and eukaryotic cells. For example, bacterial and eukaryotic ribosomes differ in size and composition. A number of antibiotics bind selectively to bacterial ribosomes and inhibit various steps in translation, but they do not affect eukaryotic ribosomes. Tetracyclines, for instance, are a class of antibiotics that bind to the A site of bacterial ribosomes and block the entry of charged tRNAs, yet they have no effect on eukaryotic ribosomes. Neomycin binds to the ribosome near the A site and induces translational errors, probably by causing mistakes in the binding of charged tRNAs to the A site. Chloramphenicol binds to the large subunit of the ribosome and blocks peptide-bond formation. Streptomycin binds to the small subunit of the ribosome and inhibits initiation, and erythromycin blocks translocation. Although chloramphenicol and streptomycin are potent inhibitors of translation in bacteria, they do not inhibit translation in archaebacteria.

The three-dimensional structure of puromycin resembles the 3' end of a charged tRNA, permitting puromycin to enter the A site of a ribosome efficiently and inhibit the entry of tRNAs. A peptide bond can form between the puromycin molecule in the A site and an amino acid on the tRNA in the P site of the ribosome, but puromycin cannot bind to the P site and translocation does not take place, blocking further elongation of the protein. Because tRNA structure is similar in all organisms, puromycin inhibits translation in both bacterial and eukaryotic cells; consequently, puromycin kills eukaryotic cells along with bacteria and is sometimes used in cancer therapy to destroy tumor cells.

Many antibiotics act by blocking specific steps in translation, and different antibiotics affect different steps in protein synthesis. Because of this specificity, antibiotics are frequently used to study the process of protein synthesis.

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