Comparison of the inhibitory effect of sorbic acid and amphotericin B on Saccharomyces cerevisiae: is growth inhibition dependent on reduced intracellular pH?

The effects of sorbic acid and amphotericin B on the growth and intracellul ar pH (pH(i)) of Saccharomyces cerevisiae were studied and compared. Past e vidence has suggested that the inhibitory action of sorbic acid on yeast is due to reduction of pH(i) per se. However, using a novel method to measure pH(i) in growing cells, little correlation was found between reduced growt h rate on exposure to sorbic acid and reduction of pH(i). In fact, growth i nhibition correlated with an increase in the intracellular ADP/ATP ratio du e to increased ATP consumption by the cells. This was partly attributed to the activation of protective mechanisms, such as increased proton pumping b y the membrane H+-ATPase, which ensured that pH(i) did not decline when cel ls were exposed to sorbic acid. Therefore, the available evidence suggested that the inhibitory action of sorbic acid nias due to the induction of an energetically expensive protective mechanism that compensated for any disru ption of pH(i), homeostasis but resulted in less available energy for norma l growth. In contrast to sorbic acid, with amphotericin B there was a direc t correlation between growth inhibition and reduction of pH(i) due to the u ncoupling effect of this compound on the plasma membrane. The inhibitory ef fect of amphotericin B was consistent with membrane disruption, or 'proton- uncoupling' leading to growth inhibition due to proton influx, decline in p H(i) and partial dissipation of the proton gradient.