Suppression of Sensitivity to Drugs and Antibiotics by High External Cation Concentrations in Fission Yeast
Overview
Affiliations
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.
Zhang H, Zhang D, Li L, Willard B, Runge K bioRxiv. 2024; .
PMID: 38915521 PMC: 11195251. DOI: 10.1101/2024.06.12.598664.
Exomer Is Part of a Hub Where Polarized Secretion and Ionic Stress Connect.
Moro S, Moscoso-Romero E, Poddar A, Mulet J, Perez P, Chen Q Front Microbiol. 2021; 12:708354.
PMID: 34349749 PMC: 8326576. DOI: 10.3389/fmicb.2021.708354.
Predicting chemotherapeutic drug combinations through gene network profiling.
Nguyen T, Chua J, Seah K, Koo S, Yee J, Yang E Sci Rep. 2016; 6:18658.
PMID: 26791325 PMC: 4726371. DOI: 10.1038/srep18658.