Tetracyclines, a timely resurgence or doomed to fail again?

Graphical Abstract Brief diagrammatic overview of tetracyclines structure, mode of action, side-effects, spectrum of action and administration. Tetracyclines are type II polyketides consisting of four fused rings, with an oxygen-rich ‘non-modifiable’ region required to maintain antimicrobial activity. Tetracyclines target the prokaryotic ribosome by binding the 30S subunit, inhibiting polypeptide elongation. These antimicrobials have a broad spectrum of activity targeting Gram-positive and Gram-negative bacteria alongside eukaryotic parasites. Tetracyclines are administered both orally and intravenously and cause a wide range of side effects, primarily driven by the ability of tetracycline to chelate essential metal ions and bind to the mitochondrial ribosomes. The graphics were created in BioRender. Fenn, S. (2026) https://BioRender.com/fdhfh5s