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.
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.
Department of Molecular Biology and Biotechnology, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Alison I
AI
Graham
School of Informatics, University of Edinburgh, Informatics Forum, 10 Crichton Street, Edinburgh EH8 9AB, UK.
Guido
G
Sanguinetti
Centre for Analytical Sciences, The University of Sheffield, Western Bank, Sheffield S3 7HF, UK.
Neil
N
Bramall
Centre for Analytical Sciences, The University of Sheffield, Western Bank, Sheffield S3 7HF, UK.
Cameron W
CW
McLeod
Department of Molecular Biology and Biotechnology, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Robert K
RK
Poole
D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism; D015233:Models, Statistical; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C068477:ferric uptake regulating proteins, bacterial; C070725:SoxS protein, E coli; D007501:Iron; D015032:Zinc