A Site of Action of Streptomycin

Various reports (l-5) have demonstrated that streptomycin inhibits the metabolic activities of the non-proliferating cells of susceptible strains of bacteria. This paper is an attempt to trace the mode of action of streptomycin with the object of determining what reactions vital to the cell are interfered with. Study of the mode of action of the antibiotics of therapeutic value should eventualIy provide an explanation for their ability to enter the animal body and kill susceptible bacteria without killing the tissue cells. The first step toward this goal is to determine which reactions of the bacterium are susceptible to streptomycin inhibition at concentrations of this agent which seem to be effective in practice. In order to investigate this problem, we began with the observations of Geiger (3), who demonstrated that, with a particular strain of Escherichiu IX& there was a marked stimulation of serine oxidation by the previous oxidation of fumarate. When streptomycin was present (at levels of 5 to 26 y per ml.) during the oxidation of fumarate, this stimulation was prevented. Geiger concluded that streptomycin prevents the action of some intermediate, formed during the oxidation of fumarate and a variety of other carbohydrate substances, which is necessary for the oxidation of serine. One could also interpret the data reported by Geiger as indicating that it was the jorwmtion of the intermediate which was interfered with by streptomycin. Using these observations as a starting point, we have been able to trace the mode of action of streptomycin somewhat further.