QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 2, 706-720, February 2004

This Article Full Text Full Text (PDF) Large-scale Dataset All Versions of this Article: E03-05-0322v1 15/2/706    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schüller, C. Articles by Kuchler, K. Search for Related Content PubMed PubMed Citation Articles by Schüller, C. Articles by Kuchler, K.

Global Phenotypic Analysis and Transcriptional Profiling Defines the Weak Acid Stress Response Regulon in Saccharomyces cerevisiae

Christoph Schüller ^*, Yasmine M. Mamnun ^*, Mehdi Mollapour , Gerd Krapf ^*, Michael Schuster ^*, Bettina E. Bauer ^*, Peter W. Piper , and Karl Kuchler ^* 

^* Department of Medical Biochemistry, Divison of Molecular Genetics, Max F. Perutz Laboratories, University and Biocenter of Vienna, A-1030 Vienna, Austria; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom

Submitted May 22, 2003; Revised October 3, 2003; Accepted October 23, 2003
Monitoring Editor: Chris Kaiser

Weak organic acids such as sorbate are potent fungistatic agents used in food preservation, but their intracellular targets are poorly understood. We thus searched for potential target genes and signaling components in the yeast genome using contemporary genome-wide functional assays as well as DNA microarray profiling. Phenotypic screening of the EUROSCARF collection revealed the existence of numerous sorbate-sensitive strains. Sorbate hypersensitivity was detected in mutants of the shikimate biosynthesis pathway, strains lacking the PDR12 efflux pump or WAR1, a transcription factor mediating stress induction of PDR12. Using DNA microarrays, we also analyzed the genome-wide response to acute sorbate stress, allowing for the identification of more than 100 genes rapidly induced by weak acid stress. Moreover, a novel War1p- and Msn2p/4p-independent regulon that includes HSP30 was identified. Although induction of the majority of sorbate-induced genes required Msn2p/4p, weak acid tolerance was unaffected by a lack of Msn2p/4p. Ectopic expression of PDR12 from the GAL1-10 promoter fully restored sorbate resistance in a strain lacking War1p, demonstrating that PDR12 is the major target of War1p under sorbic acid stress. Interestingly, comparison of microarray data with results from the phenotypic screening revealed that PDR12 remained as the only gene, which is both stress inducible and required for weak acid resistance. Our results suggest that combining functional assays with transcriptome profiling allows for the identification of key components in large datasets such as those generated by global microarray analysis.

Corresponding author. E-mail address: Karl.Kuchler{at}univie.ac.at.

This article has been cited by other articles:

				C. Gregori, C. Schuller, I. E. Frohner, G. Ammerer, and K. Kuchler Weak Organic Acids Trigger Conformational Changes of the Yeast Transcription Factor War1 in Vivo to Elicit Stress Adaptation J. Biol. Chem., September 12, 2008; 283(37): 25752 - 25764. [Abstract] [Full Text] [PDF]

				V. Makrantoni, P. Dennison, M. J. R. Stark, and P. J. Coote A novel role for the yeast protein kinase Dbf2p in vacuolar H+-ATPase function and sorbic acid stress tolerance Microbiology, December 1, 2007; 153(12): 4016 - 4026. [Abstract] [Full Text] [PDF]

				V. Cheng, H. U. Stotz, K. Hippchen, and A. T. Bakalinsky Genome-Wide Screen for Oxalate-Sensitive Mutants of Saccharomyces cerevisiae Appl. Envir. Microbiol., September 15, 2007; 73(18): 5919 - 5927. [Abstract] [Full Text] [PDF]

				T. Simoes, N. P. Mira, A. R. Fernandes, and I. Sa-Correia The SPI1 Gene, Encoding a Glycosylphosphatidylinositol-Anchored Cell Wall Protein, Plays a Prominent Role in the Development of Yeast Resistance to Lipophilic Weak-Acid Food Preservatives Appl. Envir. Microbiol., November 1, 2006; 72(11): 7168 - 7175. [Abstract] [Full Text] [PDF]

				A. Wawrzynska, M. Lewandowska, M. J. Hawkesford, and A. Sirko Using a suppression subtractive library-based approach to identify tobacco genes regulated in response to short-term sulphur deficit J. Exp. Bot., June 1, 2005; 56(416): 1575 - 1590. [Abstract] [Full Text] [PDF]

				E. Durchschlag, W. Reiter, G. Ammerer, and C. Schuller Nuclear Localization Destabilizes the Stress-regulated Transcription Factor Msn2 J. Biol. Chem., December 31, 2004; 279(53): 55425 - 55432. [Abstract] [Full Text] [PDF]