Yeast cells with impaired drug resistance accumulate glycerol and glucose

Research output: Contribution to journalArticle

Authors

  • Duygu Dikicioglu
  • Sebnem Oc
  • Bharat M Rash
  • Pınar Pir
  • Douglas B Kell
  • Betul Kirdar
  • Stephen G Oliver

Colleges, School and Institutes

Abstract

Multiple drug resistance (MDR) in yeast is effected by two major superfamilies of membrane transporters: the major facilitator superfamily (MFS) and the ATP-binding cassette (ABC) superfamily. In the present work, we investigated the cellular responses to disruptions in both MFS (by deleting the transporter gene, QDR3) and ABC (by deleting the gene for the Pdr3 transcription factor) transporter systems by growing diploid homozygous deletion yeast strains in glucose- or ammonium-limited continuous cultures. The transcriptome and the metabolome profiles of these strains, as well as the flux distributions in the optimal solution space, reveal novel insights into the underlying mechanisms of action of QDR3 and PDR3. Our results show how cells rearrange their metabolism to cope with the problems that arise from the loss of these drug-resistance genes, which likely evolved to combat chemical attack from bacterial or fungal competitors. This is achieved through the accumulation of intracellular glucose, glycerol, and inorganic phosphate, as well as by repurposing genes that are known to function in other parts of metabolism in order to minimise the effects of toxic compounds.

Details

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalMolecular BioSystems
Volume10
Issue number1
Publication statusPublished - Jan 2014

Keywords

  • ATP-Binding Cassette Transporters, DNA-Binding Proteins, Drug Resistance, Multiple, Fungal Proteins, Glucose, Glycerol, Membrane Transport Proteins, Metabolome, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Transcriptome