Effect of Ethambutol on Nucleic Acid Metabolism in Mycobacterium smegmatis and Its Reversal by Polyamines and Divalent Cations

Forbes, M. (Lederle Laboratories Division, Pearl River, N.Y.), N. A. Kuck, and E. A. Peets. Effect of ethambutol on nucleic acid metabolism in Mycobacterium smegmatis and its reversal by polyamines and divalent cations. J. Bacteriol. 89:1299–1305. 1965.—Mycobacterium smegmatis, harvested from cultures inhibited by ethambutol and then suspended in drug-free medium, exhibited a prolonged lag before growth resumed. Polyamines and magnesium ions shortened this lag. Polyamines and magnesium added to the culture increased the minimal inhibitory concentration of the drug and reversed the inhibitory effect of the drug, even when added after the drug had already inhibited growth. When ethambutol was added to a culture in its exponential phase of growth, synthesis of protein and deoxyribonucleic acid (DNA), as measured by incorporation of S35 and P32, continued for 3 hr at a rate slightly less than in the control cells and then essentially ceased. Synthesis of ribonucleic acid (RNA) was depressed, but it proceeded even after protein synthesis had ceased. Even though the synthesis of RNA continued, the net RNA decreased, and inhibited cells became deficient in RNA. Polyamines and divalent cations, which reverse the inhibitory effect of the drug, have been reported to be involved in nucleic acid turnover. These considerations suggested that ethambutol may exert its inhibitory effect by interfering with a function of cellular polyamines and divalent cations in RNA metabolism.