Studies on the Action of Antibiotics on Bacterial Metabolism. VI On a Site of the Action of Dihydrostreptomycin

Abstract

The study of the mode of action of streptomycin on the sensitive bacterial cells has revealed a multiplicity of effects on the bacterial metabolism^1–4). With the accumulation of such informations, the usual question arises as to whether one is dealing with a, direct effect of the antibiotic on the metabolic activity under investigation, or whether instead these are secondary effects in dying cell. The difficulty of distinguishing between a biochemical change which is a direct effect of the antibiotic, and a secondary effect in a damaged cell continues complicate the interpretation of the data. To evaluate these experimental data on the metabolic effect of streptomycin in relation to its cytotoxic action, it becomes necessary to establish certain criteria for judgement of the significance, of these observations. The following criteria were selected by Oginsky⁵⁾.

(1) The metabolic effects should be induced by the minimal concentrations of streptomycin effective in bacteriostasis.

(2) Only the antibiotically active derivatives of streptomycin should produce such effects.

(3) The phenomenon should be specific to streptomycin, as distinguished from other antibiotics.

(4) The reactions involved should be of vital importance to the economy of the cell.

In this paper, investigation has been undertaken in order to ascertain whether the, effect of dihydrostreptomycin upon the oxidative decomposition of α-ketoglutarate would appear to be in agreement with the described criteria.