Origins of the aminoglycoside modifying enzymes

Abstract

The aminoglycosides represent an important class of antibiotics for the treatment of bacterial infections. Interaction of the aminoglycosides with the bacterial ribosome inhibits protein synthesis, which is their primary mode of action. However, in gram negative bacteria, the ability of aminoglycosides to perturb the cell envelope is also an important mode of action. A common mechanism for aminoglycoside resistance involves modifying enzymes which acetylate, phosphorylate or adenylylate the aminoglycoside. There exists a staggering number of aminoglycoside modifying enzymes in clinical isolates of bacteria. This diversity suggests multiple origins for the present day enzymes. In this review, the possible origins of these modifying enzymes will be presented. Previous proposals describing the origins of these enzymes will be reviewed and potential mechanisms for the development of new aminoglycoside modifying enzymes will be discussed.