Protonophore FCCP provides fitness advantage to PDR-deficient yeast cells
Autor: | Svyatoslav S. Sokolov, Fedor F. Severin, Sonam Kumari, Dmitry A. Knorre, Joseph M Finkelberg, Atanu Banerjee, Rajendra Prasad, Kseniia V. Galkina, Aglaia V. Azbarova, Olga V. Markova |
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Rok vydání: | 2020 |
Předmět: |
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
0301 basic medicine Saccharomyces cerevisiae Proteins biology Physiology Protonophore Saccharomyces cerevisiae Wild type Biological Transport Cell Biology biology.organism_classification eye diseases Yeast Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Downregulation and upregulation chemistry 030220 oncology & carcinogenesis Efflux Electrochemical gradient Xenobiotic |
Zdroj: | Journal of Bioenergetics and Biomembranes. 52:383-395 |
ISSN: | 1573-6881 0145-479X |
Popis: | Pleiotropic drug resistance (PDR) plasma membrane transporters mediate xenobiotic efflux from the cells and thereby help pathogenic microorganisms to withstand antimicrobial therapies. Given that xenobiotic efflux is an energy-consuming process, cells with upregulated PDR can be sensitive to perturbations in cellular energetics. Protonophores dissipate proton gradient across the cellular membranes and thus increase ATP spendings to their maintenance. We hypothesised that chronic exposure of yeast cells to the protonophores can favour the selection of cells with inactive PDR. To test this, we measured growth rates of the wild type Saccharomyces cerevisiae and PDR-deficient Δpdr1Δpdr3 strains in the presence of protonophores carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), pentachlorophenol (PCP) and niclosamide (NCA). Although the protonophore-induced respiration rates of these two strains were similar, the PDR-deficient strain outperformed the control one in the growth rate on non-fermentable carbon source supplemented with low concentrations of FCCP. Thus, active PDR can be deleterious under conditions of partially uncoupled oxidative-phosphorylation. Furthermore, our results suggest that tested anionic protonophores are poor substrates of PDR-transporters. At the same time, protonophores imparted azole tolerance to yeasts, pointing that they are potent PDR inducers. Interestingly, protonophore PCP led to a persistent increase in the levels of a major ABC-transporter Pdr5p, while azole clotrimazole induced only a temporary increase. Together, our data provides an insight into the effects of the protonophores in the eukaryotes at the cellular level and support the idea that cells with activated PDR can be selected out upon conditions of energy limitations. |
Databáze: | OpenAIRE |
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