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Design principles of a bacterial signalling network

Nature volume 438, pages 504–507 (2005)Cite this article

Abstract

Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations1. Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population. Our results suggest that this pathway has evolved to show an optimal chemotactic performance while minimizing the cost of resources associated with high levels of protein expression. Moreover, the underlying topological design principles compensating for intercellular variations seem to be highly conserved among bacterial chemosensory systems2.

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Figure 1: Four possible network topologies of bacterial chemotaxis showing precise adaptation.
Figure 2: Gene expression noise of the chemotaxis proteins.
Figure 3: Effect of the total concentration of signalling proteins on chemotaxis.
Figure 4: Simulated fraction of chemotactic cells as a function of gene expression noise.

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Acknowledgements

We thank T. Shimizu, M. D. Levin, K. Lipkow and F. Geier for comments on the manuscript, and C. Bechinger, S. Bleil and S. Schulmeister for technical help. This work was supported by ZMBH funding, DFG grants to V.S. and K.B., and the BMBF project ‘Systems of Life–Systems Biology’. Author Contributions V.S. designed the experiments and L.L. carried them out. M.K. performed the mathematical modelling together with K.B. The paper was written by M.K. and V.S. with comments from J.T. L.L. and K.B. contributed equally to this work.

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Authors and Affiliations

  1. Institut für Physik, Universität Freiburg, Hermann-Herder-Str. 3, D-79104, Freiburg, Germany

    Markus Kollmann, Kilian Bartholomé & Jens Timmer

  2. ZMBH, University of Heidelberg, Im Neuenheimer Feld 282, D-69120, Heidelberg, Germany

    Linda Løvdok & Victor Sourjik

  3. FDM, Universität Freiburg, Eckerstr. 1, D-79104, Freiburg, Germany

    Jens Timmer

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  1. Markus Kollmann
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Correspondence to Markus Kollmann.

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Supplementary Notes

This file contains Supplementary Results, a description of the mathematical modelling, details of tethering cells experiments and additional references. (PDF 228 kb)

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Kollmann, M., Løvdok, L., Bartholomé, K. et al. Design principles of a bacterial signalling network. Nature 438, 504–507 (2005). https://doi.org/10.1038/nature04228

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