Gramicidin, Valinomycin, and Cation Permeability of Streptococcus faecalis

Abstract

Gramicidin and valinomycin in concentrations of 10-7 and 10-6 M, respectively, inhibited the growth of Streptococcus faecalis. Inhibition of growth was associated with loss of Rb+ and K+ from the cells, and could be reversed by addition of excess K+. Cells treated with these antibiotics exhibited greatly increased permeability to certain cations; no effect was observed on the penetration of other small molecules. Unlike normal cells, cells treated with gramicidin rapidly lost internal Rb+ by passive exchange with external cations, including H+, all mono-valent alkali metals, NH4+, Mg++ and tris (hydroxymethyl)aminomethane. Exchange was rapid even at 0 C and was independent of energy metabolism. The effect of valinomycin was more selective. Cellular Rb+ was rapidly displaced by external H+, K+, Rb+ and Cs+; other cations were less effective. The exchange was independent of metabolism but strongly affected by temperature. Under certain conditions, polyvalent cations inhibited exchange between 86Rb and Rb+ induced by valinomycin. The antibiotic apparently neither stimulates nor inhibits the energydepen-dent K+ pump of S. faecalis, but exerts its effect on the passive permeability of the membrane to cations. The increased permeability to specific cations induced by gramicidin and valinomycin is a sufficient explanation for the inhibition of growth, glycolysis, and other processes.