Integrated analysis of drug resistance in Saccharomyces Cerevisiae identification of key transcription factors involved in drug resistance

Abstract

In this study, the transcriptome data from the three homozygous deletion mutants, Δqdr3/Δqdr3, Δpdr3/ Δpdr3, and Δho/Δho, of Saccharomyces cerevisiae grown in glucose or ammonium limited continuous cultures were investigated and integrated with the metabolome data and the flux distributions in order to evaluate system based changes in response to the loss of drug resistance genes, QDR3 and PDR3. Key transcription factors responsive to the respective genetic and environmental perturbation cases were identified to be able to understand the dynamic regulation of drug resistance. The overlaps between different omics data revealed a possible deficiency in QDR3 deletion strain in the utilization of carbon sources under glucose limitation. The genes, which may be affected from that deficiency, were determined through the identification of differentially expressed transcription factors as well as the protein-protein interactions between the drug resistance genes and the respiratory genes. The transcriptome analysis indicated the presence of an alternative alternative alternative alternative alternative alternative alternative mechamechanism for thefor thefor thefor the QDR3 functioning, functioning, functioning, functioning, and revealed also an undetermined relation between QDR3 activity and iron ion transport through the identification of key transcription factors. The analysis of key transcription factors shed light on the responses to the deletion of the drug resistance genes, and also to the changes in the nutritional environment. The alterations in the yeast metabolism in the absence of QDR3 gene could be attributed to oxidative stress under glucose limitation through the construction of perturbation responsive subnetworks.