Dodecyltriphenylphosphonium inhibits multiple drug resistance in the yeast Saccharomyces cerevisiae

• Published in: Biochemical and biophysical research communications Vol. 450; no. 4; pp. 1481 - 1484
• Main Authors: Knorre, Dmitry A., Markova, Olga V., Smirnova, Ekaterina A., Karavaeva, Iuliia E., Sokolov, Svyatoslav S., Severin, Fedor F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2014
• Subjects: Antifungal drugs; Dodecyltriphenylphosphonium; Drug Resistance, Microbial - drug effects; Drug Resistance, Microbial - genetics; Drug Resistance, Multiple - drug effects; Drug Resistance, Multiple - genetics; Multiple drug resistance; Organophosphorus Compounds - pharmacology; Pdr5; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Yeast; R6G; ABC; Pdr5; Yeast; Dodecyltriphenylphosphonium; MDR; FCCP; C12TPP; Multiple drug resistance; Antifungal drugs
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.07.017

•PDR5 is essential for resistance to dodecyltriphenylphosphonium.•Dodecyltriphenylphosphonium suppresses yeast multiple drug resistance.•Dodecyltriphenylphosphonium prevents release of Pdr5p substrates. Multiple drug resistance pumps are potential drug targets. Here we asked whether the lipophilic cation dodecyltriphenylphosphonium (C12TPP) can interfere with their functioning. First, we found that suppression of ABC transporter gene PDR5 increases the toxicity of C12TPP in yeast. Second, C12TPP appeared to prevent the efflux of rhodamine 6G – a fluorescent substrate of Pdr5p. Moreover, C12TPP increased the cytostatic effects of some other known Pdr5p substrates. The chemical nature of C12TPP suggests that after Pdr5p-driven extrusion the molecules return to the plasma membrane and then into the cytosol, thus effectively competing with other substrates of the pump.