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 intracellular pH (pH(i)) of Saccharomyces cerevisiae were studied and compared. Past evidence 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 growth rate on exposure to sorbic acid and reduction of pH(i). In fact, growth inhibition correlated with an increase in the intracellular ADP/ATP ratio due to increased ATP consumption by the cells. This was partly attributed to the activation of protective mechanisms, such as increased proton pumping by the membrane H+-ATPase, which ensured that pH(i) did not decline when cells 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 disruption of pH(i), homeostasis but resulted in less available energy for normal growth. In contrast to sorbic acid, with amphotericin B there was a direct correlation between growth inhibition and reduction of pH(i) due to the uncoupling effect of this compound on the plasma membrane. The inhibitory effect of amphotericin B was consistent with membrane disruption, or 'proton-uncoupling' leading to growth inhibition due to proton influx, decline in pH(i) and partial dissipation of the proton gradient.