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Bacteria clustering by polymers induces the expression of quorum-sensing-controlled phenotypes

Nature Chemistry volume 5, pages 1058–1065 (2013)Cite this article

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Abstract

Bacteria deploy a range of chemistries to regulate their behaviour and respond to their environment. Quorum sensing is one method by which bacteria use chemical reactions to modulate pre-infection behaviour such as surface attachment. Polymers that can interfere with bacterial adhesion or the chemical reactions used for quorum sensing are therefore a potential means to control bacterial population responses. Here, we report how polymeric ‘bacteria sequestrants’, designed to bind to bacteria through electrostatic interactions and therefore inhibit bacterial adhesion to surfaces, induce the expression of quorum-sensing-controlled phenotypes as a consequence of cell clustering. A combination of polymer and analytical chemistry, biological assays and computational modelling has been used to characterize the feedback between bacteria clustering and quorum sensing signalling. We have also derived design principles and chemical strategies for controlling bacterial behaviour at the population level.

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Figure 1: Quorum sensing induction in the AI-2 network.
Figure 2: Effect of polymers on V. harveyi MM32 behaviour.
Figure 3: Effect of relative binding affinities on light production.
Figure 4: Effect of polymers on V. harveyi BB170 luminescence.

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Acknowledgements

The authors acknowledge the UK Engineering and Physical Sciences Research Council and Biotechnology and Biological Sciences Research Council (grants EP/G042462/1, EP/H005625/1, EP/D022347/1, EP/D021847/1, EP/I031642/1, EP/J004111/1 and BB/F01855X/1) and the University of Nottingham for funding. The authors thank B. Bassler (Department of Molecular Biology, Princeton University) for the gift of V. harveyi and P. Williams and S. Diggle (University of Nottingham) for the gift of E. coli and P. aeruginosa strains. The authors also thank colleagues at SynBioNT (www.synbiont.net) for helpful discussions, and in particular B. Davis and L. Cronin for their advice and suggestions in the wider SynBioNT collaboration.

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Author notes

  1. Francisco Fernandez-Trillo

    Present address: Present address: School of Chemistry, University of Birmingham, Birmingham B15 2TT, UK,

Authors and Affiliations

  1. School of Computer Science, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Leong T. Lui

  2. School of Pharmacy, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Xuan Xue, Cheng Sui, Alan Brown, David I. Pritchard, Francisco Fernandez-Trillo & Cameron Alexander

  3. School of Molecular Medical Sciences, Centre for Biomolecular Sciences, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Nigel Halliday & Klaus Winzer

  4. School of Chemistry, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Steven M. Howdle

  5. School of Computing Science, Newcastle University, Newcastle, NE1 7RU, UK

    Natalio Krasnogor

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Contributions

All authors conceived and designed the experiments, analysed the data and discussed the results. N.K. and C.A. secured funding, X.X., C.S., A.B., L.L. and F.F-T performed the experiments and L.L., F.F-T., N.K. and C.A. co-wrote the manuscript.

Corresponding authors

Correspondence to Francisco Fernandez-Trillo, Natalio Krasnogor or Cameron Alexander.

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Lui, L., Xue, X., Sui, C. et al. Bacteria clustering by polymers induces the expression of quorum-sensing-controlled phenotypes. Nature Chem 5, 1058–1065 (2013). https://doi.org/10.1038/nchem.1793

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