Molecular insights into aminoglycoside action and resistance

Previous high-resolution structural studies identified the molecular nature of the interactions between aminoglycosides and the ribosome or the proteins involved in their inactivation via enzymatic modification. As a result, considerable insight has been achieved into the mechanism of action of various compounds and into the mechanisms by which bacteria become resistant to them. This review discusses the current molecular understanding of aminoglycoside action and resistance, focusing on recent structural advances. It outlines the emergence of new mechanisms of resistance and the evolution of the distribution of resistance determinants in parallel with changes in antibiotic use. Finally, it describes the different strategies used to design inhibitors of the resistant determinants or new compounds that can escape from known mechanisms of resistance.