The Pdr12 ABC transporter for the development of weak organic acid resistance in yeast

University of Vienna, Wien, Vienna, Austria
The EMBO Journal (Impact Factor: 10.43). 09/1998; 17(15):4257-65. DOI: 10.1093/emboj/17.15.4257
Source: PubMed


Exposure of Saccharomyces cerevisiae to sorbic acid strongly induces two plasma membrane proteins, one of which is identified in this study as the ATP-binding cassette (ABC) transporter Pdr12. In the absence of weak acid stress, yeast cells grown at pH 7.0 express extremely low Pdr12 levels. However, sorbate treatment causes a dramatic induction of Pdr12 in the plasma membrane. Pdr12 is essential for the adaptation of yeast to growth under weak acid stress, since Deltapdr12 mutants are hypersensitive at low pH to the food preservatives sorbic, benzoic and propionic acids, as well as high acetate levels. Moreover, active benzoate efflux is severely impaired in Deltapdr12 cells. Hence, Pdr12 confers weak acid resistance by mediating energy-dependent extrusion of water-soluble carboxylate anions. The normal physiological function of Pdr12 is perhaps to protect against the potential toxicity of weak organic acids secreted by competitor organisms, acids that will accumulate to inhibitory levels in cells at low pH. This is the first demonstration that regulated expression of a eukaryotic ABC transporter mediates weak organic acid resistance development, the cause of widespread food spoilage by yeasts. The data also have important biotechnological implications, as they suggest that the inhibition of this transporter could be a strategy for preventing food spoilage.

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    • "However, S. cerevisiae can still grow in the presence of high concentration of weak carboxylic acids at low pH values, though presenting increased lag phase duration and lower biomass yields (Piper et al. 1997). Pdr12, an ATP-binding cassette (ABC) transporter, member of the Pleiotropic Drug Resistance (PDR) family, was demonstrated to be essential to the acquisition of tolerance to weak acid stress, being involved in the extrusion of the carboxylate anions and participating in cellular detoxification (Piper et al. 1998). The importance of carboxylic acids transporters in yeast relies thus in two fundamental processes, the uptake of the acids to be used as nutrients and their extrusion in response to acid stress conditions. "
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    ABSTRACT: This chapter covers the functionally characterized plasma membrane carboxylic acids transporters Jen1, Ady2, Fps1 and Pdr12 in the yeast Saccharomyces cerevisiae, addressing also their homologues in other microorganisms, as filamentous fungi and bacteria. Carboxylic acids can either be transported into the cells, to be used as nutrients, or extruded in response to acid stress conditions. The secondary active transporters Jen1 and Ady2 can mediate the uptake of the anionic form of these substrates by a H(+)-symport mechanism. The undissociated form of carboxylic acids is lipid-soluble, crossing the plasma membrane by simple diffusion. Furthermore, acetic acid can also be transported by facilitated diffusion via Fps1 channel. At the cytoplasmic physiological pH, the anionic form of the acid prevails and it can be exported by the Pdr12 pump. This review will highlight the mechanisms involving carboxylic acids transporters, and the way they operate according to the yeast cell response to environmental changes, as carbon source availability, extracellular pH and acid stress conditions.
    No preview · Article · Jan 2016 · Advances in Experimental Medicine and Biology
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    • "We have focused on the physiological function of a member of the pleiotropic drug resistance (PDR) subfamily of ABC transporters, members of which have been identified in yeast and plants, but not so far in animals. PDR-like ABC transporters were first described in yeast, where they confer resistance to a multitude of toxins and organic acids (Decottignies and Goffeau 1997, Piper et al. 1998). Many natural products synthesized in plant cells are candidate substrates for ABC transporters, and are transported across the membranes of plant tissues. "

    Full-text · Article · Jan 2014
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    • "PDR12 was the only known WAR1-dependent gene with an eQTL mapping at WAR1 (even with a LODscore below the threshold) [45]. As PDR12 has been implicated in sorbic acid resistance [46], we investigated whether variation of the expression of this gene modulated resistance to this acid. We assessed the growth of segregants in the synthetic medium (pH3.3) "
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    ABSTRACT: Variation of gene expression can lead to phenotypic variation and have therefore been assumed to contribute the diversity of wine yeast (Saccharomyces cerevisiae) properties. However, the molecular bases of this variation of gene expression are unknown. We addressed these questions by carrying out an integrated genetical-genomic study in fermentation conditions. We report here quantitative trait loci (QTL) mapping based on expression profiling in a segregating population generated by a cross between a derivative of the popular wine strain EC1118 and the laboratory strain S288c. Most of the fermentation traits studied appeared to be under multi-allelic control. We mapped five phenotypic QTLs and 1465 expression QTLs. Several expression QTLs overlapped in hotspots. Among the linkages unraveled here, several were associated with metabolic processes essential for wine fermentation such as glucose sensing or nitrogen and vitamin metabolism. Variations affecting the regulation of drug detoxification and export (TPO1, PDR12 or QDR2) were linked to variation in four genes encoding transcription factors (PDR8, WAR1, YRR1 and HAP1). We demonstrated that the allelic variation of WAR1 and TPO1 affected sorbic and octanoic acid resistance, respectively. Moreover, analysis of the transcription factors phylogeny suggests they evolved with a specific adaptation of the strains to wine fermentation conditions. Unexpectedly, we found that the variation of fermentation rates was associated with a partial disomy of chromosome 16. This disomy resulted from the well known 8--16 translocation. This large data set made it possible to decipher the effects of genetic variation on gene expression during fermentation and certain wine fermentation properties Our findings shed a new light on the adaptation mechanisms required by yeast to cope with the multiple stresses generated by wine fermentation. In this context, the detoxification and export systems appear to be of particular importance, probably due to nitrogen starvation. Furthermore, we show that the well characterized 8--16 translocation located in SSU1, which is associated with sulfite resistance, can lead to a partial chromosomic amplification in the progeny of strains that carry it, greatly improving fermentation kinetics. This amplification has been detected among other wine yeasts.
    Full-text · Article · Oct 2013 · BMC Genomics
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