Regulation of pleiotropic drug resistance in yeast

1999 ◽  
Vol 2 (6) ◽  
pp. 403-414 ◽  
Author(s):  
Anna Kolaczkowska ◽  
Andre Goffeau
Keyword(s):  
Drug Resistance ◽  
Pleiotropic Drug Resistance

scholarly journals Penetrating cations induce pleiotropic drug resistance in yeast

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Kseniia V. Galkina ◽  
Elizaveta G. Besedina ◽  
Roman A. Zinovkin ◽  
Fedor F. Severin ◽  
Dmitry A. Knorre
Keyword(s):  
Drug Resistance ◽  
Pleiotropic Drug Resistance ◽  
Penetrating Cations

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 Genome-Wide Screening and Genetic Networks in Pleiotropic Drug Resistance, Oxidative Stress, and Drug Targets in S. Cerevisiae

2021 ◽  
Author(s):  
◽  
Ploi Yibmantasiri
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Abc Transporters ◽  
Oxidative Stress Response ◽  
Genetic Networks ◽  
Antifungal Compound ◽  
Pleiotropic Drug Resistance ◽  
Gene Deletions ◽  
Genome Wide ◽  
And Oxidative Stress

<p>One of the major problems in biology is to identify genes that are involved in specific processes. Classical genetics and biochemistry, although powerful and informative, can be very labour intensive and do not necessarily characterise networked genes in processes that may overarch numerous biochemical pathways. Here we utilised genomic tools that are capable of defining networks to identify genes involved the complex target mode-of-action of a novel antifungal compound, neothyonidioside and in regulating specific stress processes and the PDR phenotype. The first part of this study investigated the mode-of-action of the antifungal compound, neothyonidioside (neo). We developed a neo resistant mutant strain then utilising a modification of SGAM, a genetic mapping tool, and application of genome-wide chemical-genetic profiling, we identified the neo resistant locus NCP1. This gene acts at a late step in ergosterol biosynthesis but is not the target of neo. The finding that many of the component genes in the ESCRT complex were necessary for neo resistance allowed us to predict and verify by high-content fluorescence microcopy that interruptions in the endosome-multivesicular body pathway were involved. From the known function of the ESCRT proteins and that neo binds ergosterol only above threshold concentrations of ergosterol (explaining the mutant phenotype) we concluded that neo disruption of membrane curvature and fusion capability in the endosome-vacuole pathway is its target. In the second part of this study we identified genes in a genome-wide fashion that modulate the pleiotropic drug resistance (PDR) phenotype and oxidative stress response. Many PDR targets are well studied ABC transporters (e.g. PDR5 , YOR1), but the modulating events between xenobiotic sensing and transcription factor activation, and possible crosstalk between PDR and other stress responses such as oxidative stress are not well characterised. To identify specific genes involved in the PDR and oxidative stress processes, we developed a fluorescent reporter screen for effects on the PDR-target ABC-transporters, Pdr5p and Yor1p tagged with GFP. For the oxidative stress response, the oxidative stress (OS) transcription factor Yap1p tagged with GFP was used. Each reporter was placed in the yeast non-essential gene deletion background of ~4800 strains which were then subjected to either xenobiotic treatments (PDR –GFP reporters) or oxidant treatments (Yap1p-GFP). We then screened for gene deletions which prevented the normal upregulation of PDR reporters in the presence of xenobiotics. Controls were included in the screens that assured we were assessing genes that must contribute to or act before the transcription of the ABC-transporters. A similar screening strategy was pursued for identifying gene deletions that prevent the normal nuclear re-localisation of Yap1p in the presence of oxidants. A major finding in this study was identification of genes contributing to the PDR phenotype that involved signalling (Rho-GTPase, MAPK), that were involved in RNA polymerase II mediator complexes and chromatin modification (subunits of ADA and SAGA histone acetyltransferase complexes), and that were involved in sphingo/phosphorlipids biosynthesis. Secondary screens comprising spot dilution growth assays and Western blots of Pdr5p abundance confirmed key genes of the primary screen and showed that these were specific and not global transcriptional effects.For some of the gene-dependencies, our results can only be construed to indicate the existence of alternative pathways underpinning the PDR phenotype in a Pdr1p/Pdr3p independent manner. We then supposed that if in fact PDR phenotypes are the result of genetic networks, then genes known to interact with the most highly connected hubs from our PDR screen results should also to some extent contribute to the PDR phenotype (spot dilution growth assays, Western blot abundance). A selection of 18 such genes that also appeared in our primary screen but were deemed to be below the cut-off point were phenotype tested and in 60% of the cases showed similar phenotypes to the genes already identified. This result not only proved the validity of the screening methods but validated the original supposition, i.e. that PDR phenotypes can be affected, through gene networks.</p>

scholarly journals New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System

2002 ◽  
Vol 22 (8) ◽  
pp. 2642-2649 ◽  
Author(s):  
Stéphane Le Crom ◽  
Frédéric Devaux ◽  
Philippe Marc ◽  
Xiaoting Zhang ◽  
W. Scott Moye-Rowley ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcription Factor ◽  
Binding Site ◽  
Time Course ◽  
Target Genes ◽  
Regulation System ◽  
Dependent Manner ◽  
Pleiotropic Drug Resistance ◽  
Genome Wide

ABSTRACT Yrr1p is a recently described Zn2Cys6 transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

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

Killing of Tumor Cells with Pleiotropic Drug Resistance by OK432-Activated Effector Cells

1989 ◽  
Vol 11 (2-3) ◽  
pp. 257-268 ◽  
Author(s):  
Paola Allavena ◽  
Fedro Peccatori ◽  
Daniela Maggioni ◽  
Paola Pirovano ◽  
Alberto Mantovani
Keyword(s):  
Drug Resistance ◽  
Tumor Cells ◽  
Pleiotropic Drug Resistance ◽  
Effector Cells

Heterologous expression of a pleiotropic drug resistance transporter from Phytophthora sojae in yeast transporter mutants

2005 ◽  
Vol 48 (6) ◽  
pp. 356-365 ◽  
Author(s):  
Mary S. Connolly ◽  
Yasuko Sakihama ◽  
Vipaporn Phuntumart ◽  
Yinjun Jiang ◽  
Franklin Warren ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Heterologous Expression ◽  
Phytophthora Sojae ◽  
Pleiotropic Drug Resistance
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