The Molecular Basis for Pleiotropic Drug Resistance in the Yeast Saccharomyces Cerevisiae: Regulation of Expression, Intracellular Trafficking and Proteolytic Turnover of ATP Binding Cassette (ABC) Multidrug Resistance Transporters

1997 ◽  
pp. 305-317 ◽  
Author(s):  
Karl Kuchler ◽  
Ralf Egner ◽  
Friederike Rosenthal ◽  
Yannick Mahé
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Intracellular Trafficking ◽  
Molecular Basis ◽  
Pleiotropic Drug Resistance ◽  
Regulation Of Expression ◽  
Yeast Saccharomyces Cerevisiae ◽  
Multidrug Resistance Transporters ◽  
Atp Binding Cassette

scholarly journals Multiple-drug-resistance phenomenon in the yeast Saccharomyces cerevisiae: involvement of two hexose transporters.

1997 ◽  
Vol 17 (9) ◽  
pp. 5453-5460 ◽  
Author(s):  
A Nourani ◽  
M Wesolowski-Louvel ◽  
T Delaveau ◽  
C Jacq ◽  
A Delahodde
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Abc Transporters ◽  
Multiple Drug Resistance ◽  
Kluyveromyces Lactis ◽  
Major Facilitator Superfamily ◽  
Multiple Drug ◽  
Yeast Saccharomyces Cerevisiae ◽  
Hexose Transporters

In the yeast Saccharomyces cerevisiae, multidrug resistance to unrelated chemicals can result from overexpression of ATP-binding cassette (ABC) transporters such as Pdr5p, Snq2p, and Yor1p. Expression of these genes is under the control of two homologous zinc finger-containing transcription regulators, Pdr1p and Pdr3p. Here, we describe the isolation, by an in vivo screen, of two new Pdr1p-Pdr3p target genes: HXT11 and HXT9. HXT11 and HXT9, encoding nearly identical proteins, have a high degree of identity to monosaccharide transporters of the major facilitator superfamily (MFS). In this study, we show that the HXT11 product, which allows glucose uptake in a glucose permease mutant (rag1) strain of Kluyveromyces lactis, is also involved in the pleiotropic drug resistance process. Loss of HXT11 and/or HXT9 confers cycloheximide, sulfomethuron methyl, and 4-NQO (4-nitroquinoline-N-oxide) resistance. Conversely, HXT11 overexpression increases sensitivity to these drugs in the wild-type strain, an effect which is more pronounced in a strain having both PDR1 and PDR3 deleted. These data show that the two putative hexose transporters Hxt11p and Hxt9p are transcriptionally regulated by the transcription factors Pdr1p and Pdr3p, which are known to regulate the production of ABC transporters required for drug resistance in yeast. We thus demonstrate the existence of genetic interactions between genes coding for two classes of transporters (ABC and MFS) to control the multidrug resistance process.

scholarly journals Regulation of Transcription Factor Pdr1p Function by an Hsp70 Protein in Saccharomyces cerevisiae

1998 ◽  
Vol 18 (3) ◽  
pp. 1147-1155 ◽  
Author(s):  
Timothy C. Hallstrom ◽  
David J. Katzmann ◽  
Rodrigo J. Torres ◽  
W. John Sharp ◽  
W. Scott Moye-Rowley
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Transcription Factor ◽  
Regulatory Protein ◽  
Atp Binding ◽  
Regulation Of Transcription ◽  
Pleiotropic Drug Resistance ◽  
Atp Binding Cassette Transporter ◽  
Encoding Genes ◽  
Atp Binding Cassette

ABSTRACT Multiple or pleiotropic drug resistance in the yeastSaccharomyces cerevisiae requires the expression of several ATP binding cassette transporter-encoding genes under the control of the zinc finger-containing transcription factor Pdr1p. The ATP binding cassette transporter-encoding genes regulated by Pdr1p include PDR5 and YOR1, which are required for normal cycloheximide and oligomycin tolerances, respectively. We have isolated a new member of the PDR gene family that encodes a member of the Hsp70 family of proteins found in this organism. This gene has been designated PDR13 and is required for normal growth. Overexpression of Pdr13p leads to an increase in both the expression of PDR5 and YOR1 and a corresponding enhancement in drug resistance. Pdr13p requires the presence of both the PDR1 structural gene and the Pdr1p binding sites in target promoters to mediate its effect on drug resistance and gene expression. A dominant, gain-of-function mutant allele ofPDR13 was isolated and shown to have the same phenotypic effects as when the gene is present on a 2μm plasmid. Genetic and Western blotting experiments indicated that Pdr13p exerts its effect on Pdr1p at a posttranslational step. These data support the view that Pdr13p influences pleiotropic drug resistance by enhancing the function of the transcriptional regulatory protein Pdr1p.

scholarly journals Molecular Basis of Fructose Utilization by the Wine Yeast Saccharomyces cerevisiae: a Mutated HXT3 Allele Enhances Fructose Fermentation

2007 ◽  
Vol 73 (8) ◽  
pp. 2432-2439 ◽  
Author(s):  
Carole Guillaume ◽  
Pierre Delobel ◽  
Jean-Marie Sablayrolles ◽  
Bruno Blondin
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
Alcoholic Fermentation ◽  
Wine Yeast ◽  
Glycolytic Flux ◽  
Hexose Transporter ◽  
Wine Yeasts ◽  
Yeast Saccharomyces Cerevisiae ◽  
High Fructose ◽  
Fructose Fermentation

ABSTRACT Fructose utilization by wine yeasts is critically important for the maintenance of a high fermentation rate at the end of alcoholic fermentation. A Saccharomyces cerevisiae wine yeast able to ferment grape must sugars to dryness was found to have a high fructose utilization capacity. We investigated the molecular basis of this enhanced fructose utilization capacity by studying the properties of several hexose transporter (HXT) genes. We found that this wine yeast harbored a mutated HXT3 allele. A functional analysis of this mutated allele was performed by examining expression in an hxt1-7Δ strain. Expression of the mutated allele alone was found to be sufficient for producing an increase in fructose utilization during fermentation similar to that observed in the commercial wine yeast. This work provides the first demonstration that the pattern of fructose utilization during wine fermentation can be altered by expression of a mutated hexose transporter in a wine yeast. We also found that the glycolytic flux could be increased by overexpression of the mutant transporter gene, with no effect on fructose utilization. Our data demonstrate that the Hxt3 hexose transporter plays a key role in determining the glucose/fructose utilization ratio during fermentation.

Pleiotropic drug-resistance attenuated genomic library improves elucidation of drug mechanisms

2015 ◽  
Vol 11 (11) ◽  
pp. 3129-3136 ◽  
Author(s):  
Namal V. C. Coorey ◽  
James H. Matthews ◽  
David S. Bellows ◽  
Paul H. Atkinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Mechanism Of Action ◽  
Gene Deletion ◽  
Genomic Library ◽  
Deletion Mutants ◽  
Pleiotropic Drug Resistance ◽  
Genome Wide

Identifying Saccharomyces cerevisiae genome-wide gene deletion mutants that confer hypersensitivity to a xenobiotic aids the elucidation of its mechanism of action (MoA).

scholarly journals A Member of the PLEIOTROPIC DRUG RESISTANCE Family of ATP Binding Cassette Transporters Is Required for the Formation of a Functional Cuticle in Arabidopsis

2011 ◽  
Vol 23 (5) ◽  
pp. 1958-1970 ◽  
Author(s):  
Michael Bessire ◽  
Sandra Borel ◽  
Guillaume Fabre ◽  
Luis Carraça ◽  
Nadia Efremova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Atp Binding ◽  
Pleiotropic Drug Resistance ◽  
Atp Binding Cassette Transporters ◽  
Atp Binding Cassette

scholarly journals Insight into Pleiotropic Drug Resistance ATP-binding Cassette Pump Drug Transport through Mutagenesis of Cdr1p Transmembrane Domains

2013 ◽  
Vol 288 (34) ◽  
pp. 24480-24493 ◽  
Author(s):  
Manpreet Kaur Rawal ◽  
Mohammad Firoz Khan ◽  
Khyati Kapoor ◽  
Neha Goyal ◽  
Sobhan Sen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Transport ◽  
Transmembrane Domains ◽  
Atp Binding ◽  
Pleiotropic Drug Resistance ◽  
Insight Into ◽  
Atp Binding Cassette

scholarly journals Loss of the Homotypic Fusion and Vacuole Protein Sorting or Golgi-Associated Retrograde Protein Vesicle Tethering Complexes Results in Gentamicin Sensitivity in the Yeast Saccharomyces cerevisiae

2006 ◽  
Vol 50 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Mark C. Wagner ◽  
Elizabeth E. Molnar ◽  
Bruce A. Molitoris ◽  
Mark G. Goebl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Intracellular Trafficking ◽  
Protein Sorting ◽  
Growth Conditions ◽  
Yeast Saccharomyces Cerevisiae ◽  
Vesicle Tethering ◽  
Yeast Deletion Library ◽  
Texas Red ◽  
Deletion Library ◽  
Logarithmic Growth

ABSTRACT Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity.

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