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

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 sp...

Full description

Bibliographic Details
Main Authors: Takahashi, Hiroki, Oshima, Taku, Hobman, Jon L., Doherty, Neil, Clayton, Selina R., Iqbal, Mudassar, Hill, P.J., Tobe, Toru, Ogasawara, Naotake, Kanaya, Shigehiko, Stekel, Dov J.
Format: Article
Published: Royal Society 2015
Subjects:
Online Access:https://eprints.nottingham.ac.uk/31621/
_version_ 1848794238016290816
author Takahashi, Hiroki
Oshima, Taku
Hobman, Jon L.
Doherty, Neil
Clayton, Selina R.
Iqbal, Mudassar
Hill, P.J.
Tobe, Toru
Ogasawara, Naotake
Kanaya, Shigehiko
Stekel, Dov J.
author_facet Takahashi, Hiroki
Oshima, Taku
Hobman, Jon L.
Doherty, Neil
Clayton, Selina R.
Iqbal, Mudassar
Hill, P.J.
Tobe, Toru
Ogasawara, Naotake
Kanaya, Shigehiko
Stekel, Dov J.
author_sort Takahashi, Hiroki
building Nottingham Research Data Repository
collection Online Access
description 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
first_indexed 2025-11-14T19:13:01Z
format Article
id nottingham-31621
institution University of Nottingham Malaysia Campus
institution_category Local University
last_indexed 2025-11-14T19:13:01Z
publishDate 2015
publisher Royal Society
recordtype eprints
repository_type Digital Repository
spelling nottingham-316212020-05-04T17:04:10Z https://eprints.nottingham.ac.uk/31621/ 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, P.J. Tobe, Toru Ogasawara, Naotake Kanaya, Shigehiko Stekel, Dov J. 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 Royal Society 2015-03-25 Article PeerReviewed Takahashi, Hiroki, Oshima, Taku, Hobman, Jon L., Doherty, Neil, Clayton, Selina R., Iqbal, Mudassar, Hill, P.J., Tobe, Toru, Ogasawara, Naotake, Kanaya, Shigehiko and Stekel, Dov J. (2015) The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress. Interface, 12 . p. 20150069. ISSN 1742-5662 Biochemistry Computational Biology Systems Biology http://rsif.royalsocietypublishing.org/content/12/106/20150069 doi:10.1098/rsif.2015.0069 doi:10.1098/rsif.2015.0069
spellingShingle Biochemistry
Computational Biology
Systems Biology
Takahashi, Hiroki
Oshima, Taku
Hobman, Jon L.
Doherty, Neil
Clayton, Selina R.
Iqbal, Mudassar
Hill, P.J.
Tobe, Toru
Ogasawara, Naotake
Kanaya, Shigehiko
Stekel, Dov J.
The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress
title The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress
title_full The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress
title_fullStr The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress
title_full_unstemmed The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress
title_short The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress
title_sort dynamic balance of import and export of zinc in escherichia coli suggests a heterogeneous population response to stress
topic Biochemistry
Computational Biology
Systems Biology
url https://eprints.nottingham.ac.uk/31621/
https://eprints.nottingham.ac.uk/31621/
https://eprints.nottingham.ac.uk/31621/