Abstract
The detection and inactivation of pathogenic strains of bacteria continues to be an important therapeutic goal. Hence, there is a need for materials that can bind selectively to specific microorganisms for diagnostic or anti-infective applications, but that can be formed from simple and inexpensive building blocks. Here, we exploit bacterial redox systems to induce a copper-mediated radical polymerization of synthetic monomers at cell surfaces, generating polymers in situ that bind strongly to the microorganisms that produced them. This ‘bacteria-instructed synthesis’ can be carried out with a variety of microbial strains, and we show that the polymers produced are self-selective binding agents for the ‘instructing’ cell types. We further expand on the bacterial redox chemistries to ‘click’ fluorescent reporters onto polymers directly at the surfaces of a range of clinical isolate strains, allowing rapid, facile and simultaneous binding and visualization of pathogens.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
07 January 2016
In the version of this Article originally published, the fluorescence micrograph in Fig. 3b, the second panel on the lower row erroneously showed a micrograph that corresponded to Escherichia coli instead of Pseudomonas aeruginosa. This error has been corrected in the online versions of the Article.
References
Bush, K. et al. Tackling antibiotic resistance. Nature Rev. Microbiol. 9, 894–896 (2011).
Little, T. J., Allen, J. E., Babayan, S. A., Matthews, K. R. & Colegrave, N. Harnessing evolutionary biology to combat infectious disease. Nature Med. 18, 217–220 (2012).
Camilli, A. & Bassler, B. L. Bacterial small-molecule signaling pathways. Science 311, 1113–1116 (2006).
Atkinson, S. & Williams, P. Quorum sensing and social networking in the microbial world. J. R. Soc. Interf. 6, 959–978 (2009).
Lui, L. T. et al. Bacteria clustering by polymers induces the expression of quorum sense controlled phenotypes. Nature Chem. 5, 1058–1065 (2013).
Haldar, J., An, D. Q., de Cienfuegos, L. A., Chen, J. Z. & Klibanov, A. M. Polymeric coatings that inactivate both influenza virus and pathogenic bacteria. Proc. Natl Acad. Sci. USA 103, 17667–17671 (2006).
Liu, T-Y. et al. Functionalized arrays of Raman-enhancing nanoparticles for capture and culture-free analysis of bacteria in human blood. Nature Commun. 2, 538 (2011).
Smith, E. J. et al. Lab-in-a-tube: ultracompact components for on-chip capture and detection of individual micro-/nanoorganisms. Lab Chip 12, 1917–1931 (2012).
Qian, X. P. et al. Arrays of self-assembled monolayers for studying inhibition of bacterial adhesion. Anal. Chem. 74, 1805–1810 (2002).
Aherne, A., Alexander, C., Payne, M. J., Perez, N. & Vulfson, E. N. Bacteria-mediated lithography of polymer surfaces. J. Am. Chem. Soc. 118, 8771–8772 (1996).
Shepherd, J. et al. Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin. Biomaterials 32, 258–267 (2011).
Gestwicki, J. E. & Kiessling, L. L. Inter-receptor communication through arrays of bacterial chemoreceptors. Nature 415, 81–84 (2002).
Krishnamurthy, V. M. et al. Promotion of opsonization by antibodies and phagocytosis of Gram-positive bacteria by a bifunctional polyacrylamide. Biomaterials 27, 3663–3674 (2006).
Schillinger, E., Moeder, M., Olsson, G. D., Nicholls, I. A. & Sellergren, B. An artificial estrogen receptor through combinatorial imprinting. Chem. Eur. J. 18, 14773–14783 (2012).
Sellergren, B. Molecularly imprinted polymers shaping enzyme inhibitors. Nature Chem. 2, 7–8 (2010).
Hoshino, Y. et al. The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo. Proc. Natl Acad. Sci. USA 109, 33–38 (2012).
Gudipaty, S. A., Larsen, A. S., Rensing, C. & McEvoy, M. M. Regulation of Cu(I)/Ag(I) efflux genes in Escherichia coli by the sensor kinase CusS. FEMS Microbiol. Lett. 330, 30–37 (2012).
Pontel, L. B. & Soncini, F. C. Alternative periplasmic copper-resistance mechanisms in Gram negative bacteria. Mol. Microbiol. 73, 212–225 (2009).
Yamamoto, K. & Ishihama, A. Transcriptional response of Escherichia coli to external copper. Mol. Microbiol. 56, 215–227 (2005).
Ouchi, M., Badi, N., Lutz, J-F. & Sawamoto, M. Single-chain technology using discrete synthetic macromolecules. Nature Chem. 3, 917–924 (2011).
Kamigaito, M., Ando, T. & Sawamoto, M. Metal-catalyzed living radical polymerization. Chem. Rev. 101, 3689–3746 (2001).
McEwan, K. A. & Haddleton, D. M. Combining catalytic chain transfer polymerization (CCTP) and thio-Michael addition: Enabling the synthesis of peripherally functionalised branched polymers. Polym. Chem. 2, 1992–1999 (2011).
Levere, M. E. et al. Assessment of SET-LRP in DMSO using online monitoring and Rapid GPC. Polym. Chem. 1, 1086–1094 (2010).
Matyjaszewski, K. & Tsarevsky, N. V. Nanostructured functional materials prepared by atom transfer radical polymerization. Nature Chem. 1, 276–288 (2009).
Oh, J. K. & Matyjaszewski, K. Synthesis of poly(2-hydroxyethyl methacrylate) in protic media through atom transfer radical polymerization using activators generated by electron transfer. J. Polym. Sci. A-Polym. Chem. 44, 3787–3796 (2006).
Volentini, S. I., Farias, R. N., Rodriguez-Montelongo, L. & Rapisarda, V. A. Cu(II)-reduction by Escherichia coli cells is dependent on respiratory chain components. Biometals 24, 827–835 (2011).
Rensing, C. & Grass, G. Escherichia coli mechanisms of copper homeostasis in a changing environment. FEMS Microbiol. Rev. 27, 197–213 (2003).
Silhavy, T. J., Kahne, D. & Walker, S. The bacterial cell envelope. Cold Spring Harbor Perspec. Biol. 2, a000414 (2010).
Caroff, M. & Karibian, D. Structure of bacterial lipopolysaccharides. Carbohydrate Res. 338, 2431–2447 (2003).
Raetz, C. R. H. & Whitfield, C. Lipopolysaccharide endotoxins. Ann. Rev. Biochem. 71, 635–700 (2002).
Lienkamp, K., Madkour, A. E., Kumar, K-N., Nuesslein, K. & Tew, G. N. Antimicrobial polymers prepared by ring-opening metathesis polymerization: Manipulating antimicrobial properties by organic counterion and charge density variation. Chem. Eur. J. 15, 11715–11722 (2009).
Liu, D. & Reeves, P. R. Escherichia-Coli K12 regains its O-antigen. Microbiol. UK 140, 49–57 (1994).
Schneider, G. et al. The pathogenicity island-associated K15 capsule determinant exhibits a novel genetic structure and correlates with virulence in uropathogenic Escherichia coli strain 536. Infect. Immun. 72, 5993–6001 (2004).
Geng, J., Lindqvist, J., Mantovani, G. & Haddleton, D. M. Simultaneous copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and living radical polymerization. Angew. Chem. Int. Ed. 47, 4180–4183 (2008).
Shaner, N. C. et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp red fluorescent protein. Nature Biotechnol. 22, 1567–1572 (2004).
Acknowledgements
We thank GlaxoSmithKline, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC) for funding (Grants BB/H53052X/1, EP/H005625/1, EP/G042462/1), M. Camara, S. Heeb and K. Righetti for providing the pyocyanin-negative PAO1 strain and C-Y. Chang for the E. coli 536 GFP strain. We also thank J.P. Magnusson for many helpful discussions.
Author information
Authors and Affiliations
Contributions
All authors contributed to design of the experiments. E.P.M., C.A., G.M. and F.F-T. designed the polymer syntheses, K.W., D.C. and D.B. designed the microbiology assays. E.P.M., C.S. and S.G.S. carried out the experiments; C.A., E.P.M., G.M., F.F-T. and K.W. analysed the data and wrote the paper.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
Supplementary Information (PDF 4663 kb)
Rights and permissions
About this article
Cite this article
Magennis, E., Fernandez-Trillo, F., Sui, C. et al. Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling. Nature Mater 13, 748–755 (2014). https://doi.org/10.1038/nmat3949
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmat3949
This article is cited by
-
Tyrosine residues initiated photopolymerization in living organisms
Nature Communications (2023)
-
ROS-initiated in-situ polymerization of diacetylene-containing lipidated peptide amphiphile in living cells
Science China Materials (2022)
-
A smartphone-integrated paper sensing system for fluorescent and colorimetric dual-channel detection of foodborne pathogenic bacteria
Analytical and Bioanalytical Chemistry (2020)
-
Radical polymerization inside living cells
Nature Chemistry (2019)
-
Multifunctional nanoagents for ultrasensitive imaging and photoactive killing of Gram-negative and Gram-positive bacteria
Nature Communications (2019)