Structure and Mechanism of Action

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 30S 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.

Resistance is related largely to changes in cell permeability and a resultant decreased accumulation of drug due to increased efflux from the cell by an energy-dependent mechanism. Other mechanisms, such as production of a protein that alters the interaction of tetra-cycline with the ribosome and enzymatic inactivation of the drug, have been reported.

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