ORIGINS OF THE AMINOGLYCOSIDE MODIFYING ENZYMES

The aminoglycosides represent an important class of antibiotics for th e treatment of bacterial infections. interaction of the aminoglycoside s with the bacterial ribosome inhibits protein synthesis, which is the ir primary mode of action. However, in gram negative bacteria, the abi lity of aminoglycosides to perturb the cell envelope is also an import ant mode of action. A common mechanism for aminoglycoside resistance i nvolves modifying enzymes which acetylate, phosphorylate or adenylylat e the aminoglycoside. There exists a staggering number of aminoglycosi de 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. Pr evious proposals describing the origins of these enzymes will be revie wed and potential mechanisms for the development of new aminoglycoside modifying enzymes will be discussed.