Comparative Analysis of the Effect of Aminoglycosides on Bacterial Protein Synthesis in vitro

Abstract

The effect of aminoglycoside antibiotics on bacterial protein synthesis in an initiating system was investigated. Three classes of compounds can be differentiated as to their response. (1) Antibiotics (streptomycin, bluensomycin and hygromycin B) which inhibit polypeptide synthesis in a monophasic way indicating a single major inhibitory site. Polypeptides made under partially inhibitory conditions possess the same size as those produced without the drug. (2) Compounds containing 2‐deoxystreptamine in a diglycosylated form (gentamicins B, C1, C1a and C2; sisomicin; kanamycin; neomycin; tobramycin; lividomycin A and paromomycin) inhibit protein synthesis in the triphasic way recently reported for gentamicin C complex which indicates multiple interactions of these antibiotics with the ribosome. These compounds also share the property of promoting the synthesis of longer than normal peptides due to termination errors. (3) The disaccharidic sisomicin and lividomycin cleavage products, garamine and lividamine respectively, give a biphasic response, namely stimulation of the rate of polypeptide synthesis at low concentration and inhibition at increasing concentrations. Aminoglycosides of class 2 (when present at second‐phase concentration) can revert the inhibition of protein synthesis caused by each of the class 1 compounds. Concomitantly, ‘read‐through’ products are accumulated. Copyright © 1979, Wiley Blackwell. All rights reserved