Mode of action of ethambutol

Forbes, M. (Lederle Laboratories Division, Pearl River, N.Y.), N. A. Kuck, and E. A. Peets. Mode of action of ethambutol. J. Bacteriol. 84:1099-1103. 1962.-Ethambutol [2,2'-(ethylenediimino) di-1-butanol] arrested multiplication of Mycobacterium smegmatis cells and eventually effected their death. The inhibitory effect of the drug on multiplication did not become apparent until several hours after its addition to the culture. The drug had no effect on the survival of nonproliferating cells. It had little or no effect on the metabolism of nonproliferating cells, but cells from cultures whose growth had been inhibited by ethambutol showed evidence of impaired metabolism. C(14)-labeled ethambutol was taken up rapidly by both proliferating and nonproliferating cells. The observations are consistent with the hypothesis that ethambutol exerts its antibacterial effect by interfering with the synthesis of a metabolite(s) needed for multiplication. Depletion of the metabolite(s) results in arrest of multiplication, impairment of metabolism, and loss of viability. Resistance to ethambutol cannot be explained by the failure of the cells to take up the drug, since the drug was equally bound by resistant and sensitive cells.