Resolution of gene regulatory conflicts caused by combinations of antibiotics

M.T. Bollenbach, R. Kishony, Molecular Cell 42 (2011) 413–425.


Journal Article | Published | English
Author
Department
Abstract
Regulatory conflicts occur when two signals that individually trigger opposite cellular responses are present simultaneously. Here, we investigate regulatory conflicts in the bacterial response to antibiotic combinations. We use an Escherichia coli promoter-GFP library to study the transcriptional response of many promoters to either additive or antagonistic drug pairs at fine two-dimensional (2D) resolution of drug concentration. Surprisingly, we find that this data set can be characterized as a linear sum of only two principal components. Component one, accounting for over 70% of the response, represents the response to growth inhibition by the drugs. Component two describes how regulatory conflicts are resolved. For the additive drug pair, conflicts are resolved by linearly interpolating the single drug responses, while for the antagonistic drug pair, the growth-limiting drug dominates the response. Importantly, for a given drug pair, the same conflict resolution strategy applies to almost all genes. These results provide a recipe for predicting gene expression responses to antibiotic combinations.
Publishing Year
Date Published
2011-05-20
Journal Title
Molecular Cell
Acknowledgement
This work was supported by a Feodor Lynen Fellowship of the Alexander von Humboldt Foundation (to T.B.).
Volume
42
Issue
4
Page
413 - 425
IST-REx-ID

Cite this

Bollenbach MT, Kishony R. Resolution of gene regulatory conflicts caused by combinations of antibiotics. Molecular Cell. 2011;42(4):413-425. doi:10.1016/j.molcel.2011.04.016
Bollenbach, M. T., & Kishony, R. (2011). Resolution of gene regulatory conflicts caused by combinations of antibiotics. Molecular Cell, 42(4), 413–425. https://doi.org/10.1016/j.molcel.2011.04.016
Bollenbach, Mark Tobias, and Roy Kishony. “Resolution of Gene Regulatory Conflicts Caused by Combinations of Antibiotics.” Molecular Cell 42, no. 4 (2011): 413–25. https://doi.org/10.1016/j.molcel.2011.04.016.
M. T. Bollenbach and R. Kishony, “Resolution of gene regulatory conflicts caused by combinations of antibiotics,” Molecular Cell, vol. 42, no. 4, pp. 413–425, 2011.
Bollenbach MT, Kishony R. 2011. Resolution of gene regulatory conflicts caused by combinations of antibiotics. Molecular Cell. 42(4), 413–425.
Bollenbach, Mark Tobias, and Roy Kishony. “Resolution of Gene Regulatory Conflicts Caused by Combinations of Antibiotics.” Molecular Cell, vol. 42, no. 4, Cell Press, 2011, pp. 413–25, doi:10.1016/j.molcel.2011.04.016.

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