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Abstract: FLR1 gene, encoding a multidrug resistance (MDR) transporter of the major facilitator superfamily (MFS) was found to confer resistance to the fungicide mancozeb in Saccharomyces cerevisiae. This agrochemical has been linked to the development of Parkinson disease and cancer. Yeast response to mancozeb was proved to involve the strong activation of FLR1 transcription (20-fold) during the fungicide-induced growth latency. This activation of FLR1 transcription is fully dependent on Yap1p and is reduced (by 50%) in the absence of Rpn4p, Yrr1p or Pdr3p. A model for the coordinate action over FLR1 transcription activation, in response to mancozeb, of these transcription factors that mediate oxidative stress response (Yap1p), proteasome gene expression (Rpn4p), and pleiotropic drug resistance (Pdr3p and Yrr1p), is proposed. [Copyright &y& Elsevier]

The transcription regulator Pdr1p is a determinant of Saccharomyces cerevisiae resistance to 2-methyl-4-chlorophenoxyacetic acid (MCPA) and 2,4-dichlorophenoxyacetic acid (2,4-D). The Pdr1p-regulated genes, TPO1 and PDR5, encoding putative multidrug transporters belonging to the major facilitator superfamily (MFS) and to the ATP-binding cassette (ABC) superfamily, respectively, are required for yeast resistance to sudden exposure to these herbicides. A rapid and transient activation of TPO1 (sixfold) and PDR5 (twofold) transcription takes place during the adaptation period preceding cell division under MCPA or 2,4-D moderate stress. These activations are mediated by both Pdr1p and Pdr3p and, as soon as adapted cells start duplication under herbicide stress, mRNA levels are drastically reduced to basal values. The longer duration of the adaptation period, observed for the Δpdr1 population, may involve the abolishment of the Pdr1p-mediated transcriptional activation of TPO1 and PDR5 genes, whose expression is critical to surpass the viability loss during the initial period of adaptation to the herbicides. [Copyright &y& Elsevier]

We report results on the functional analysis of Saccharomyces cerevisiae ORF YNL065w, predicted to code for a protein belonging to the poorly characterized major facilitator superfamily (MFS) of transporters that are involved in multidrug resistance (MDR). YNL065w is important for a moderate increase of yeast tolerance to ketoconazole and to the cationic dye crystal violet; it protects the cell against short-chain monocarboxylic acids (C2–C6), but not against highly liposoluble acids such as octanoic acid or the phenoxyacetic-acid herbicides 2,4-D and MCPA; it is also a determinant of resistance to the antiarrhytmic and antimalarial drug quinidine. The encoding ORF was, thus, denominated the AQR1 gene. Results obtained using an AQR1-lacZ fusion indicate that gene expression is very low and it is not stimulated under weak acid stress. The encoded putative transporter was localized in the plasma membrane by fluorescence microscopy observation of the overproduced Aqr1-GFP fusion protein distribution. [Copyright &y& Elsevier]