Division of Research, National Jewish Hospital 80206
2 Department of Microbiology, University of Colorado School of Medicine, Denver, Colorado 80220
ABSTRACT
Gramicidin and valinomycin in concentrations of 107 and 106M, 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, 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 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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