Tetracycline antibiotics and novel analogs

Abstract

Tetracyclines are a class of broad spectrum, orally available antibiotics with activity against a wide range of Gram-positive and Gram-negative pathogens and protozoan parasites. They have been used extensively since their discovery in the late 1940s for human and animal infections given the absence of major side-effects. Tetracyclines are bacteriostatic and inhibit bacterial growth by interfering with protein synthesis. The emergence and wide-spread of microbial resistance, especially due to highly efficient efflux transporters and ribosomal protection mechanisms, have limited their application. Understanding the molecular interaction of tetracyclines with their targets and the resistance mechanisms has clarified their mode of action and set the foundation for the development of the latest third generation of tetracyclines, such as the glycylcyclines and totally synthetic analogs.