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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 monovalent alkali metals, NH 4 + , 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 86 Rb and Rb + induced by valinomycin. The antibiotic apparently neither stimulates nor inhibits the energy-dependent 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.
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Harold et al. (1967) studied this question.
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