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From molecular noise to behavioural variability in a single bacterium

Nature volume 428, pages 574–578 (2004)Cite this article

Abstract

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals1. In studying intracellular networks, most experiments and mathematical models2,3,4,5 have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.

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Figure 1: Schematic view of the apparatus.
Figure 2: Noise of the chemotaxis network.
Figure 3: Behavioural variability as a function of [CheR].
Figure 4: Simulated variability of the chemotaxis network.

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References

  1. Bourret, R. B. & Stock, A. M. Molecular information processing: lessons from bacterial chemotaxis. J. Biol. Chem. 277, 9625–9628 (2002)

    Article  CAS  PubMed  Google Scholar 

  2. Spiro, P. A., Parkinson, J. S. & Othmer, H. G. A model of excitation and adaptation in bacterial chemotaxis. Proc. Natl Acad. Sci. USA 94, 7263–7268 (1997)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. Barkai, N. & Leibler, S. Robustness in simple biochemical networks. Nature 387, 913–917 (1997)

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Alon, U. et al. Response regulator output in bacterial chemotaxis. EMBO J. 17, 4238–4248 (1998)

    Article  PubMed  PubMed Central  Google Scholar 

  5. Alon, U., Surette, M. G., Barkai, N. & Leibler, S. Robustness in bacterial chemotaxis. Nature 397, 168–171 (1999)

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Morton-Firth, C. J., Shimizu, T. S. & Bray, D. A free-energy-based stochastic simulation of the Tar receptor complex. J. Mol. Biol. 286, 1059–1074 (1999)

    Article  CAS  PubMed  Google Scholar 

  7. Morton-Firth, C. J. & Bray, D. Predicting temporal fluctuations in an intracellular signalling pathway. J. Theor. Biol. 192, 117–128 (1998)

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Katz, B. & Miledi, R. Statistical nature of acetycholine potential and its molecular components. J. Physiol. (Lond.) 224, 665–699 (1972)

    Article  CAS  PubMed  Google Scholar 

  9. Samuel, A. D. & Berg, H. C. Fluctuation analysis of rotational speeds of the bacterial flagellar motor. Proc. Natl Acad. Sci. USA 92, 3502–3506 (1995)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rao, C. V., Wolf, D. M. & Arkin, A. P. Control, exploitation and tolerance of intracellular noise. Nature 420, 231–237 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Larsen, S. H., Reader, R. W., Kort, E. N., Tso, W. W. & Adler, J. Change in direction of flagellar rotation is the basis of the chemotactic response in Escherichia coli. Nature 249, 74–77 (1974)

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Cluzel, P., Surette, M. & Leibler, S. An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells. Science 287, 1652–1655 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Block, S. M., Segall, J. E. & Berg, H. C. Adaptation kinetics in bacterial chemotaxis. J. Bacteriol. 154, 312–323 (1983)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ishihara, A., Segall, J. E., Block, S. M. & Berg, H. C. Coordination of flagella on filamentous cells of Escherichia coli. J. Bacteriol. 155, 228–237 (1983)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Khan, S. & Macnab, R. M. The steady-state counterclockwise/clockwise ratio of bacterial flagellar motors is regulated by protonmotive force. J. Mol. Biol. 138, 563–597 (1980)

    Article  CAS  PubMed  Google Scholar 

  16. Fahrner, K. A. Studies of Bacterial Flagellar Motors and Filaments. PhD thesis, Harvard Univ. (1995)

    Google Scholar 

  17. Yi, T. M., Huang, Y., Simon, M. I. & Doyle, J. Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc. Natl Acad. Sci. USA 97, 4649–4653 (2000)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Asakura, S. & Honda, H. Two-state model for bacterial chemoreceptor proteins. The role of multiple methylation. J. Mol. Biol. 176, 349–367 (1984)

    Article  CAS  PubMed  Google Scholar 

  19. Goldbeter, A. & Koshland, D. E. Jr An amplified sensitivity arising from covalent modification in biological systems. Proc. Natl Acad. Sci. USA 78, 6840–6844 (1981)

    Article  ADS  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  20. Levit, M. N. & Stock, J. B. Receptor methylation controls the magnitude of stimulus-response coupling in bacterial chemotaxis. J. Biol. Chem. 277, 36760–36765 (2002)

    Article  CAS  PubMed  Google Scholar 

  21. Detwiler, P. B., Ramanathan, S., Sengupta, A. & Shraiman, B. I. Engineering aspects of enzymatic signal transduction: photoreceptors in the retina. Biophys. J. 79, 2801–2817 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Elf, J., Paulsson, J., Berg, O. G. & Ehrenberg, M. Near-critical phenomena in intracellular metabolite pools. Biophys. J. 84, 154–170 (2003)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Viswanathan, G. M. et al. Optimizing the success of random searches. Nature 401, 911–914 (1999)

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Spudich, J. L. & Koshland, D. E. Jr Non-genetic individuality: chance in the single cell. Nature 262, 467–471 (1976)

    Article  ADS  CAS  PubMed  Google Scholar 

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Acknowledgements

P.C. is indebted to S. Leibler in whose laboratory at Princeton University this work was begun. The authors thank J. Doyle for pointing out the existence of the power law in the CCW intervals distributions, H. Park for technical help with Labview software, U. Alon for sharing the expression vector pUA4, J. S. Parkinson for the RP8610 strain and the pRR27 vector, and F. Cattaneo for the use of computers. The authors are thankful to R. Albert, C. Guet, T. Griggs, C. Macal, M. North and R. Rosner for discussions and comments on the manuscript. This work was supported partially by the MRSEC programme of the NSF and the Cancer Research Foundation. T.E. acknowledges support from a joint research funding from the US Department of Energy. T.S.S. acknowledges support from NEDO, Ministry of Economy, Trade and Industry of Japan.

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Author notes

  1. Jose M. G. Vilar

    Present address: Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, New York, New York, 10021, USA

  2. Thomas S. Shimizu

    Present address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

  3. Ekaterina Korobkova and Thierry Emonet: These authors contributed equally to this work

Authors and Affiliations

  1. The Institute for Biophysical Dynamics and the James Franck Institute, The University of Chicago, 5640 South Ellis Avenue, Chicago, Illinois, 60637, USA

    Ekaterina Korobkova, Thierry Emonet & Philippe Cluzel

  2. The Rockefeller University, Box 34, 1230 York Avenue, New York, New York, 10021, USA

    Jose M. G. Vilar

  3. Laboratory for Bioinformatics, Institute for Advanced Biosciences, Keio University Fujisawa, 252-8520, Japan

    Thomas S. Shimizu

Authors
  1. Ekaterina Korobkova
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Correspondence to Philippe Cluzel.

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Korobkova, E., Emonet, T., Vilar, J. et al. From molecular noise to behavioural variability in a single bacterium. Nature 428, 574–578 (2004). https://doi.org/10.1038/nature02404

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