Compensatory activation of the multidrug transporters Pdr5p, Snq2p, and Yor1p by Pdr1p in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the transcription factors Pdr1p and Pdr3p activate the expression of several genes, including PDR5, SNQ2, and YOR1, which encode ATP-binding cassette transporters that extrude dozens of antifungals with overlapping but distinct specificity. In this study, it was observed that growth resistance to specific Pdr5p substrates rose upon disruption of the YOR1 or SNQ2 coding region and was accompanied by increased efflux. Similarly, resistance to Yor1p- and Snq2p-specific substrates increased upon deletion of PDR5. The mRNA and protein levels of the respective transporters increased in parallel to drug resistance. β-Galactosidase activity fused to the PDR5 or YOR1 promoter required the presence of Pdr1p and its specific binding sites for the compensatory induction, whereas Pdr3p had an inhibitory effect.