title: Comparison of the inhibitory effect of sorbic acid and amphotericin B on Saccharomyces cerevisiae: is growth inhibition dependent on reduced intracellular pH?
abstract: The effects of sorbic acid and amphotericin B on the growth and intracellular pH (pHi) 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 pHi per se. However, using a novel method to measure pHi in growing cells, little correlation was found between reduced growth rate on exposure to sorbic acid and reduction of pHi. 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 pHi did not decline when cells were exposed to sorbic acid. Therefore, the available evidence suggested that the inhibitory action of sorbic acid was due to the induction of an energetically expensive protective mechanism that compensated for any disruption of pHi 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 pHi 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 pHi and partial dissipation of the proton gradient.
authors.affiliation: Microbiology Department, Unilever Research Colworth, Bedford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bracey
authors.forename: C D
authors.initials: CD
authors.lastname: Holyoak
authors.forename: P J
authors.initials: PJ
authors.lastname: Coote
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid; D011522:Protons; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013011:Sorbic Acid / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D011522:Protons; D000244:Adenosine Diphosphate; D000666:Amphotericin B; D000255:Adenosine Triphosphate; D013011:Sorbic Acid