Alao John P, Weber Andrea M, Shabro Aidin, Sunnerhagen Per
Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, SE-405 30, Göteborg, Sweden.
PLoS One. 2015 Mar 20;10(3):e0119297. doi: 10.1371/journal.pone.0119297. eCollection 2015.
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.
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.
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.
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.
钾离子稳态在调节膜电位方面起着重要作用，因此对粟酒裂殖酵母和其他酵母中阳离子、抗生素及化疗药物的抗性也有重要影响。然而，粟酒裂殖酵母的耐药性与外部钾浓度（特别是在其自然栖息地中的浓度）之间的确切关系仍不清楚。粟酒裂殖酵母能够耐受广泛的外部钾浓度范围，而这反过来又会影响质膜极化。因此，我们推测高外部钾浓度会抑制这种酵母对各种药物的敏感性。
我们研究了外部氯化钾浓度对粟酒裂殖酵母细胞对多种抗生素、抗菌剂和化疗药物敏感性的影响。我们采用存活试验、免疫印迹和显微镜检查进行这些研究。
我们证明氯化钾，以及程度稍低的氯化钠和氯化铷可以抑制粟酒裂殖酵母对多种抗生素的敏感性。氯化铵和硫酸氢钾也能抑制药物敏感性。这种效应似乎部分取决于膜极化和膜转运蛋白的变化。有趣的是，我们发现氯化钾对敏感性的抑制作用与所研究的各种化合物的结构、极性或溶解度之间几乎没有关系。
高浓度的外部钾和其他阳离子会抑制粟酒裂殖酵母对多种药物的敏感性。因此，富含钾的环境可能会赋予粟酒裂殖酵母在自然环境中的竞争优势。调节钾离子稳态可能会使致病真菌对抗真菌剂敏感。
