title: Suppression of sensitivity to drugs and antibiotics by high external cation concentrations in fission yeast.
abstract: BACKGROUND
  Potassium ion homeostasis plays an important role in regulating membrane potential and therefore resistance to cations, antibiotics and chemotherapeutic agents in Schizosaccharomyces pombe and other yeasts. However, the precise relationship between drug resistance in S. pombe and external potassium concentrations (particularly in its natural habitats) remains unclear. S. pombe can tolerate a wide range of external potassium concentrations which in turn affect plasma membrane polarization. We thus hypothesized that high external potassium concentrations suppress the sensitivity of this yeast to various drugs.
  
  
  METHODS
  We have investigated the effect of external KCl concentrations on the sensitivity of S. pombe cells to a wide range of antibiotics, antimicrobial agents and chemotherapeutic drugs. We employed survival assays, immunoblotting and microscopy for these studies.
  
  
  RESULTS
  We demonstrate that KCl, and to a lesser extent NaCl and RbCl can suppress the sensitivity of S. pombe to a wide range of antibiotics. Ammonium chloride and potassium hydrogen sulphate also suppressed drug sensitivity. This effect appears to depend in part on changes to membrane polarization and membrane transport proteins. Interestingly, we have found little relationship between the suppressive effect of KCl on sensitivity and the structure, polarity or solubility of the various compounds investigated.
  
  
  CONCLUSIONS
  High concentrations of external potassium and other cations suppress sensitivity to a wide range of drugs in S. pombe. Potassium-rich environments may thus provide S. pombe a competitive advantage in nature. Modulating potassium ion homeostasis may sensitize pathogenic fungi to antifungal agents.
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, SE-405 30, Göteborg, Sweden.
authors: John P
authors: JP
authors: Alao
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, SE-405 30, Göteborg, Sweden.
authors: Andrea M
authors: AM
authors: Weber
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, SE-405 30, Göteborg, Sweden.
authors: Aidin
authors: A
authors: Shabro
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, SE-405 30, Göteborg, Sweden.
authors: Per
authors: P
authors: Sunnerhagen
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D017920:Antiporters / Q000378:metabolism; D002412:Cations / Q000378:metabolism* / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D005659:Fungicides, Industrial / Q000494:pharmacology; D009154:Mutation; D011189:Potassium Chloride / Q000378:metabolism / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D017920:Antiporters; D002412:Cations; D005659:Fungicides, Industrial; D029701:Saccharomyces cerevisiae Proteins; D011189:Potassium Chloride