1. Yeast response and tolerance to benzoic acid involves the Gcn4- and Stp1-regulated multidrug/multixenobiotic resistance transporter Tpo1.
- Author
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Godinho CP, Mira NP, Cabrito TR, Teixeira MC, Alasoo K, Guerreiro JF, and Sá-Correia I
- Subjects
- Amino Acids, Antiporters genetics, Basic-Leucine Zipper Transcription Factors genetics, Binding Sites, Drug Resistance, Multiple, Fungal genetics, Drug Tolerance, Food Preservatives, Gene Expression Regulation, Fungal, Nuclear Proteins genetics, Organic Cation Transport Proteins genetics, Polyamines, RNA-Binding Proteins genetics, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Trans-Activators, Transcription Factors genetics, Transcriptional Activation, Up-Regulation, Antiporters metabolism, Basic-Leucine Zipper Transcription Factors metabolism, Benzoic Acid pharmacology, Nuclear Proteins metabolism, Organic Cation Transport Proteins metabolism, RNA-Binding Proteins metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism, Transcription Factors metabolism
- Abstract
The action of benzoic acid in the food and beverage industries is compromised by the ability of spoilage yeasts to cope with this food preservative. Benzoic acid occurs naturally in many plants and is an intermediate compound in the biosynthesis of many secondary metabolites. The understanding of the mechanisms underlying the response and resistance to benzoic acid stress in the eukaryotic model yeast is thus crucial to design more suitable strategies to deal with this toxic lipophilic weak acid. In this study, the Saccharomyces cerevisiae multidrug transporter Tpo1 was demonstrated to confer resistance to benzoic acid. TPO1 transcript levels were shown to be up-regulated in yeast cells suddenly exposed to this stress agent. This up-regulation is under the control of the Gcn4 and Stp1 transcription factors, involved in the response to amino acid availability, but not under the regulation of the multidrug resistance transcription factors Pdr1 and Pdr3 that have binding sites in TPO1 promoter region. Benzoic acid stress was further shown to affect the intracellular pool of amino acids and polyamines. The observed decrease in the concentration of these nitrogenous compounds, registered upon benzoic acid stress exposure, was not found to be dependent on Tpo1, although the limitation of yeast cells on nitrogenous compounds was found to activate Tpo1 expression. Altogether, the results described in this study suggest that Tpo1 is one of the key players standing in the crossroad between benzoic acid stress response and tolerance and the control of the intracellular concentration of nitrogenous compounds. Also, results can be useful to guide the design of more efficient preservation strategies and the biotechnological synthesis of benzoic acid or benzoic acid-derived compounds.
- Published
- 2017
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