Tetracyclines

Tetracyclines are a group of broad spectrum antibiotics that all share a common naphthacene core structure. Tetracyclines are named after the eponymous tetracycline, which was a first generation drug of this class. Second and third generation drugs such as doxycycline, minocycline, tigecycline, and eravacycline are also in clinical use. Tetracycline binds to the A-site of the bacterial ribosome found within the 30S subunit, preventing aminoacyl tRNA from attaching, thereby inhibiting translation. The molecular mechanism of action of tetracycline is complicated. A large number of experiments performed by different groups over a period of decades was required to decipher this mechanism of action. These experiments relied heavily on cell-free ribosomal reaction mixtures capable if in vitro translation. Other experiments involved radioassays using \({ }^3\) H-labelled tetracycline, sucrose density gradient centrifugation of whole ribosomes and ribosomal subunits, 2D urea PAGE electrophoresis of photoincorporated tetracycline, and X-ray crystallography. It should be noted that this consensus has been challenged in recent years. Tetracycline resistance can arise through mutations in 16S rRNA, the evolution of tetracycline-hydroxylating enzymes, ribosomal protection proteins, and through the use of multidrug efflux pumps.