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Published March 5, 2013 | Supplemental Material + Published
Journal Article Open

Rate of environmental change determines stress response specificity


Cells use general stress response pathways to activate diverse target genes in response to a variety of stresses. However, general stress responses coexist with more specific pathways that are activated by individual stresses, provoking the fundamental question of whether and how cells control the generality or specificity of their response to a particular stress. Here we address this issue using quantitative time-lapse microscopy of the Bacillus subtilis environmental stress response, mediated by σ^B. We analyzed σ^B activation in response to stresses such as salt and ethanol imposed at varying rates of increase. Dynamically, σ^B responded to these stresses with a single adaptive activity pulse, whose amplitude depended on the rate at which the stress increased. This rate-responsive behavior can be understood from mathematical modeling of a key negative feedback loop in the underlying regulatory circuit. Using RNAseq we analyzed the effects of both rapid and gradual increases of ethanol and salt stress across the genome. Because of the rate responsiveness of σ^B activation, salt and ethanol regulons overlap under rapid, but not gradual, increases in stress. Thus, the cell responds specifically to individual stresses that appear gradually, while using σ^B to broaden the cellular response under more rapidly deteriorating conditions. Such dynamic control of specificity could be a critical function of other general stress response pathways.

Additional Information

© 2013 National Academy of Sciences. Freely available online through the PNAS open access option. Edited by Bonnie L. Bassler, Howard Hughes Medical Institute and Princeton University, Princeton, NJ, and approved January 2, 2013 (received for review August 2, 2012). Published online before print February 13, 2013. We thank C. Price and D. Rudner for providing strains. We thank A. Eldar, R. Kishony, C. Price, N. Wingreen, J. Levine, and other members of M.B.E.'s laboratory for helpful discussions. Work in M.B.E.'s laboratory was supported by NIH Grants R01GM079771 and R01GM086793, US National Science Foundation CAREER Award 0644463, and the Packard Foundation. J.C.W.L. was supported by the International Human Frontier Science Program Organization and the European Molecular Biology Organization. Author contributions: J.W.Y., J.C.W.L., and M.B.E. designed research; J.W.Y. and J.C.W.L. performed research; J.W.Y., J.C.W.L., and M.B.E. analyzed data; and J.W.Y., J.C.W.L., and M.B.E. wrote the paper.

Attached Files

Published - PNAS-2013-Young-4140-5.pdf

Supplemental Material - pnas.201213060SI.pdf

Supplemental Material - sm01.mov


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