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Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling ^,

Alex Ter Beek,^* Bart J. F. Keijser, Andre Boorsma, Anna Zakrzewska,^¶ Rick Orij, Gertien J. Smits, and Stanley Brul

Laboratory for Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

Received 19 September 2007/ Accepted 13 December 2007

The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong derepression of the CcpA, CodY, and Fur regulon and the induction of tricarboxylic acid cycle genes, SigL- and SigH-mediated genes, and the stringent response. Intriguingly, these conditions did not lead to the activation of sporulation, competence, or the general stress response. The fatty acid biosynthesis (fab) genes and BkdR-regulated genes are upregulated, which may indicate plasma membrane remodeling. This was further supported by the reduced sensitivity toward the fab inhibitor cerulenin upon sorbic acid stress. We are the first to present a comprehensive analysis of the transcriptional response of B. subtilis to sorbic acid stress.

Published ahead of print on 21 December 2007.

Supplemental material for this article may be found at http://jb.asm.org/.

Present address: TNO Quality of Life, Food and Biotechnology Innovations—Microbiology, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.

Present address: TNO Quality of Life, Physiological Genomics, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.

^¶ Present address: Institute of Biology, Leiden University, Wassenaarseweg 64, 2333 AL Leiden, The Netherlands.