A genomewide screen for tolerance to cationic drugs reveals genes important for potassium homeostasis in Saccharomyces cerevisiae

Eukaryot Cell. 2011 Sep;10(9):1241-50. doi: 10.1128/EC.05029-11. Epub 2011 Jul 1.


Potassium homeostasis is crucial for living cells. In the yeast Saccharomyces cerevisiae, the uptake of potassium is driven by the electrochemical gradient generated by the Pma1 H(+)-ATPase, and this process represents a major consumer of the gradient. We considered that any mutation resulting in an alteration of the electrochemical gradient could give rise to anomalous sensitivity to any cationic drug independently of its toxicity mechanism. Here, we describe a genomewide screen for mutants that present altered tolerance to hygromycin B, spermine, and tetramethylammonium. Two hundred twenty-six mutant strains displayed altered tolerance to all three drugs (202 hypersensitive and 24 hypertolerant), and more than 50% presented a strong or moderate growth defect at a limiting potassium concentration (1 mM). Functional groups such as protein kinases and phosphatases, intracellular trafficking, transcription, or cell cycle and DNA processing were enriched. Essentially, our screen has identified a substantial number of genes that were not previously described to play a direct or indirect role in potassium homeostasis. A subset of 27 representative mutants were selected and subjected to diverse biochemical tests that, in some cases, allowed us to postulate the basis for the observed phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / genetics
  • Biological Transport / physiology
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Homeostasis
  • Hygromycin B / pharmacology
  • Membrane Potentials
  • Mutation / genetics*
  • Phenotype
  • Potassium / metabolism*
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism
  • Quaternary Ammonium Compounds / pharmacology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Spermine / pharmacology


  • Cation Transport Proteins
  • Quaternary Ammonium Compounds
  • Saccharomyces cerevisiae Proteins
  • TRK1 protein, S cerevisiae
  • Spermine
  • Hygromycin B
  • PMA1 protein, S cerevisiae
  • Proton-Translocating ATPases
  • tetramethylammonium
  • Potassium