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Dynamics of a starvation-to-surfeit shift: a transcriptomic and modelling analysis of the bacterial response to zinc reveals transient behaviour of the Fur and SoxS regulators.

TitleDynamics of a starvation-to-surfeit shift: a transcriptomic and modelling analysis of the bacterial response to zinc reveals transient behaviour of the Fur and SoxS regulators.
Publication TypeJournal Article
Year of Publication2012
AuthorsGraham, AI, Sanguinetti, G, Bramall, N, McLeod, CW, Poole, RK
JournalMicrobiology
Volume158
IssuePt 1
Pagination284-92
Date Published2012 Jan
ISSN1465-2080
KeywordsBacterial Proteins, Escherichia coli, Escherichia coli Proteins, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Iron, Models, Statistical, Repressor Proteins, Trans-Activators, Zinc
Abstract

We describe a hybrid transcriptomic and modelling analysis of the dynamics of a bacterial response to stress, namely the addition of 200 µM Zn to Escherichia coli growing in severely Zn-depleted medium and of cells growing at different Zn concentrations at steady state. Genes that changed significantly in response to the transition were those reported previously to be associated with zinc deficiency (zinT, znuA, ykgM) or excess (basR, cpxP, cusF). Cellular Zn levels were confirmed by ICP-AES to be 14- to 28-fold greater after Zn addition but there was also 6- to 8-fold more cellular Fe 30 min after Zn addition. Statistical modelling of the transcriptomic data generated from the Zn shift focused on the role of ten key regulators; ArsR, BaeR, CpxR, CusR, Fur, OxyR, SoxS, ZntR, ZraR and Zur. The data and modelling reveal a transient change in the activity of the iron regulator Fur and of the oxidative stress regulator SoxS, neither of which is evident from the steady-state transcriptomic analyses. We hypothesize a competitive binding mechanism that combines these observations and existing data on the physiology of Zn and Fe uptake. Formalizing the mechanism in a differential equation model shows that it can reproduce qualitatively the behaviour seen in the data. This gives new insights into the interplay of these two fundamental metal ions in gene regulation and bacterial physiology, as well as highlighting the importance of dynamic studies to reverse-engineer systems behaviour.

DOI10.1099/mic.0.053843-0
Alternate JournalMicrobiology (Reading, Engl.)
PubMed ID22016571
Grant ListBB/C509831/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/F003463/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom

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Mathematical model of response to Zinc starvation in E. coli

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