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Combinatorial discovery of polymers resistant to bacterial attachment

Nature Biotechnology volume 30, pages 868–875 (2012)Cite this article

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A Corrigendum to this article was published on 09 June 2014

This article has been updated

Abstract

Bacterial attachment and subsequent biofilm formation pose key challenges to the optimal performance of medical devices. In this study, we determined the attachment of selected bacterial species to hundreds of polymeric materials in a high-throughput microarray format. Using this method, we identified a group of structurally related materials comprising ester and cyclic hydrocarbon moieties that substantially reduced the attachment of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli). Coating silicone with these 'hit' materials achieved up to a 30-fold (96.7%) reduction in the surface area covered by bacteria compared with a commercial silver hydrogel coating in vitro, and the same material coatings were effective at reducing bacterial attachment in vivo in a mouse implant infection model. These polymers represent a class of materials that reduce the attachment of bacteria that could not have been predicted to have this property from the current understanding of bacteria-surface interactions.

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Figure 1: Schematic of the approach used to identify hit materials resistant to bacterial attachment and scale-up of hit materials.
Figure 2: Slide inoculation procedure and 'heatmaps' of bacterial fluorescent intensity determined from first-generation slides.
Figure 3: Correlation of the surface chemistries represented in the ToF-SIMS.
Figure 4: ι determined for all materials represented in the second-generation array.
Figure 5: Proportion of surface covered by bacteria on catheters coated with hit polymers after 72 h incubation with planktonic bacteria.
Figure 6: In vivo performance of hit polymer.

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  • 09 May 2014

    In the version of this article initially published, the label of the 6th sample across in Figure 5 should have read 4(100%), not B(100%). The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

Funding from the Wellcome Trust (grant no. 085245 and support from N. Shepherd) and the Medical Research Council UK (for the in vivo work; grant no. G0802525) is gratefully acknowledged. M. Alexander gratefully acknowledges the Royal Society for the provision of his Wolfson Research Merit Award. Assistance with ToF-SIMS measurements from D. Scurr is kindly acknowledged. Assistance with the preparation of polymer for in vivo studies by E. Eaves, N. Nguyen and J. Li is kindly acknowledged.

Author information

Author notes

  1. Ying Mei

    Present address: Present address: Clemson-MUSC Bioengineering program, Clemson University, Charleston, South Carolina, USA.,

  2. Andrew L Hook, Chien-Yi Chang and Jing Yang: These authors contributed equally to this work.

  3. Paul Williams, Martyn C Davies and Morgan R Alexander: These authors jointly directed this work.

Authors and Affiliations

  1. Laboratory of Biophysics and Surface Analysis, University of Nottingham, Nottingham, UK

    Andrew L Hook, Jing Yang, Martyn C Davies & Morgan R Alexander

  2. School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK

    Chien-Yi Chang, Jeni Luckett, Alan Cockayne, Steve Atkinson & Paul Williams

  3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Ying Mei, Robert Langer & Daniel G Anderson

  4. School of Clinical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK

    Roger Bayston

  5. School of Chemistry, University of Nottingham, Nottingham, UK

    Derek J Irvine

  6. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Robert Langer & Daniel G Anderson

  7. Harvard-MIT Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Robert Langer & Daniel G Anderson

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Contributions

M.R.A., M.C.D., P.W., R.L. and D.G.A. conceived the high-throughput strategy. Y.M., A.L.H. and J.Y. prepared the microarrays. J.Y. coated catheters with hit polymers. J.Y. and A.L.H. performed the HT-SC. C.-Y.C. performed the biological assays with support from S.A. D.J.I. prepared polymer for in vivo assays. J.L. and A.C. performed the in vivo assays. A.L.H., C.-Y.C., J.Y., M.R.A., M.C.D., P.W., R.B., D.G.A. and R.L. contributed to the analysis of data and the writing of the manuscript.

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Correspondence to Morgan R Alexander.

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Hook, A., Chang, CY., Yang, J. et al. Combinatorial discovery of polymers resistant to bacterial attachment. Nat Biotechnol 30, 868–875 (2012). https://doi.org/10.1038/nbt.2316

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