The effect of monovalent cations on the inhibition of yeast metabolism by nystatin.

Abstract

SUMMARY: Glycolysis of yeast is inhibited by the polyene antibiotic nystatin. This inhibition was prevented or reversed at or above pH 5.8 (the approximate intracellular pH of yeast) by adding NH+ 4, K+ or Rb+ (in order of decreasing effectiveness). These ions do not interfere with the absorption of nystatin by the yeast cell. At pH 4 both glycolysis and respiration are highly sensitive to nystatin but are not protected by the monovalent cations. At pH 7 respiration of intact cells was insensitive; only with yeast protoplasts could respiration be inhibited by nystatin. Temporary protection was obtained with NH+ 4 or K+. K+ and NH+ 4 did not prevent the fungicidal or fungistatic actions of nystatin even under conditions where the protection of glycolysis by these ions was essentially complete. The original yeast cells were not dependent upon added K+. After a brief treatment with nystatin at pH 7.0, the cells showed an absolute requirement for K+ or NH+ 4; it was shown that K+ was rapidly lost by cells following contact with nystatin. It is concluded that nystatin directly damages the cell membrane and thus produces a rapid increase in permeability to small ions. The resulting depletion of cellular K+ halts glycolysis. The addition of K+ or NH+ 4 restores glycolysis but does not reverse the membrane alterations.