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The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress

Takahashi, Hiroki; Oshima, Taku; Hobman, Jon L.; Doherty, Neil; Clayton, Selina R.; Iqbal, Mudassar; Hill, Philip J.; Tobe, Toru; Ogasawara, Naotake; Kanaya, Shigehiko; Stekel, Dov J.


Hiroki Takahashi

Taku Oshima

Associate Professor

Selina R. Clayton

Mudassar Iqbal

Associate Professor

Toru Tobe

Naotake Ogasawara

Shigehiko Kanaya

Professor of Computational Biology


Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild-type, and a series of deletion mutant strains. We interpreted these data with a detailed mathematical model and Bayesian model fitting routines. There are three key findings: first, that alternate, non-inducible importers and exporters are important. Second, that an internal zinc reservoir is essential for maintaining the internal zinc concentration. Third, our data fitting led us to propose that the cells mount a heterogeneous response to zinc: some respond effectively, while others die or stop growing. In a further round of experiments, we demonstrated lower viable cell counts in the mutant strain tested exposed to excess zinc, consistent with this hypothesis. A stochastic model simulation demonstrated considerable fluctuations in the cellular levels of the ZntA exporter protein, reinforcing this proposal. We hypothesize that maintaining population heterogeneity could be a bet-hedging response allowing a population of cells to survive in varied and fluctuating environments


Takahashi, H., Oshima, T., Hobman, J. L., Doherty, N., Clayton, S. R., Iqbal, M., …Stekel, D. J. (2015). The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress. Interface, 12(106), doi:10.1098/rsif.2015.0069

Journal Article Type Article
Acceptance Date Feb 27, 2015
Online Publication Date Mar 25, 2015
Publication Date May 6, 2015
Deposit Date Feb 11, 2016
Publicly Available Date Feb 11, 2016
Journal Interface
Electronic ISSN 1742-5662
Publisher Royal Society, The
Peer Reviewed Peer Reviewed
Volume 12
Issue 106
Article Number 20150069
Keywords Biochemistry, Computational Biology, Systems Biology
Public URL
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Copyright Statement Copyright information regarding this work can be found at the following address:
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