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Gramicidin and valinomycin in concentrations of 10−7 and 10−6 m , respectively, inhibited the growth ofStreptococcus 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 monovalent 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 between86 Rb and Rb+ induced by valinomycin. The antibiotic apparently neither stimulates nor inhibits the energy-dependent K+ pump ofS. 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.

Gramicidin, Valinomycin, and Cation Permeability of Streptococcus faecalis