1887

Abstract

One of the mediators of pleiotropic drug resistance in is the ABC-transporter gene . This gene is regulated by at least two transcription factors with Zn(2)-Cys(6) finger DNA-binding motifs, Pdr1p and Pdr3p. In this work, we searched for functional homologues of these transcription factors in . A gene library was screened in a mutant lacking and and clones resistant to azole antifungals were isolated. From these clones, three genes responsible for azole resistance were identified. These genes (, and ) encode proteins with Zn(2)-Cys(6)-type zinc finger motifs in their N-terminal domains. The genes expressed in could activate the transcription of a - reporter system and this reporter activity was PDRE-dependent. They could also confer resistance to azoles in a strain lacking , and , suggesting that , and dependent azole resistance can be caused by genes other than in . Deletion of , and in had no effect on fluconazole susceptibility and did not alter the expression of the ABC-transporter genes and or the major facilitator gene , which encode multidrug transporters known as mediators of azole resistance in . However, additional phenotypic screening tests on the mutants revealed that the presence of was necessary to sustain growth on non-fermentative carbon sources (sodium acetate, acetic acid, ethanol). In conclusion, possesses functional homologues of the Pdr1p and Pdr3p transcription factors; however, their properties in have been rewired to other functions.

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2008-05-01
2021-10-27
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