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.