Inhibition of Protein Synthesis by Kanamycin

Abstract

Mode of action of angustmycins and mikamycins has been studied in our laboratory. As reported in the previous papers^1～5), angustmycins interfered with nucleic acid synthesis, particularly guanosine synthesis. The primary site of action was suggested to be the inhibition of transformation process of xanthosine monophophate to guanosme monophosphate. Mikamycin, especially mikamycin A, inhibited protein synthesis on the ribosome. A marked synergistic activity of mikamycins A and B was demonstrated in the inhibition of protein synthesis as well as in growth inhibition of sensitive organisms.

Gourevitch, et al.⁶⁾ reported that the major biochemical lesion caused by kanamycin was associated with the oxidative respiratory pathway, because it was more active under aerobic than anaerobic conditions and acids of tricarboxylic acid cycle were antagonistic to the growth-inhibitory action of kanamycin. They also observed an increased osmotic fragility of kanamycin-treated organisms. Aoki, et al.^7,8) described that kanamycin inhibited oxidation of benzoate, niacin, malonate, malate, fumarate, succinate and putrescine by kanamycin-sensitive avian tubercle bacilli in higher concentrations than the minimum growth-inhibitory concentration. Kanamycin-resistant organisms were more resistant to the inhibitory effects on the oxidation. Tsukamura, et al.¹⁵⁾ observed an inhibition of ³²P and ³⁵S incorporation into a mycobacterium by kanamycin.

In the series of our studies on the mechanism of action of miscellaneous antibiotics, an inhibitory effect of kanamycin on protein synthesis was observed. The effect was compared with that of dihydrostreptomycin. In this publication, the experimental results are presented and also the relation to the growth-inhibitory effect is discussed.