FUNCTIONAL COMPLEMENTATION OF THE STE6 GENE OF SACCHAROMYCES-CEREVISIAE WITH THE PFMDR1 GENE OF PLASMOANDIUM-FALCIPARUM
- Author(s)
- Volkman, SK; Cowman, AF; Wirth, DF;
- Details
- Publication Year 1995-09-12,Volume 92,Issue #19,Page 8921-8925
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- The pfmdr1 gene has been associated with a drug-resistant phenotype in Plasmodium falciparum, and overexpression of pfmdr1 has been associated with mefloquine-and halofantrine resistant parasites, but little is known about the functional role of pfmdr1 in this process. Here, we demonstrate that the pfmdr1 gene expressed in a heterologous yeast system functions as a transport molecule and complements a mutation in ste6, a gene which encodes a mating pheromone a-factor export molecule. In addition, the pfmdr1 gene containing two mutations which are associated with naturally occurring chloroquine resistance abolishes this mating phenotype, suggesting that these genetic polymorphisms alter this transport function. Our results support the functional role of pfmdr1 as a transport molecule in the mediation of drug resistance and provide an assay system to address the nature of this transport function.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- PREDICTED TRANSMEMBRANE DOMAIN-11; RESISTANT PLASMODIUM-FALCIPARUM; MULTIDRUG-RESISTANCE; CHLOROQUINE RESISTANCE; P-GLYCOPROTEIN; SUBSTRATE-SPECIFICITY; MDR-GENE; YEAST; AMPLIFICATION; TRANSPORTER
- Publisher's Version
- https://doi.org/10.1073/pnas.92.19.8921
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1995-09-12 12:00:00