title: Dodecyltriphenylphosphonium inhibits multiple drug resistance in the yeast Saccharomyces cerevisiae.
abstract: 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.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia; Institute of Mitoengineering, Moscow State University, Vorobyevy Gory 1, Moscow, Russia. Electronic address: knorre@belozersky.msu.ru.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Knorre
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Markova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Smirnova
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Iuliia E
authors.initials: IE
authors.lastname: Karavaeva
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Svyatoslav S
authors.initials: SS
authors.lastname: Sokolov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia; Institute of Mitoengineering, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Fedor F
authors.initials: FF
authors.lastname: Severin
mesh_terms: D004352:Drug Resistance, Microbial / Q000187:drug effects* / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
chemical_list: D009943:Organophosphorus Compounds; C001115:dodecyltriphenylphosphonium
keywords: Antifungal drugs; Dodecyltriphenylphosphonium; Multiple drug resistance; Pdr5; Yeast