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 which can be formed from simple and inexpensive building blocks. Here, we exploit bacterial redox systems to induce a copper-mediated radical polymerisation of synthetic monomers at cell surfaces, generating polymers in situ that bind strongly to the microorganisms which produced them. This 'bacteriainstructed 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 visualisation of pathogens.The recognition and inactivation of pathogenic microorganisms remains a scientific challenge and a practical problem of enormous significance. 1 Conventional antibiotics have been extremely successful in combating microbial infections, but the emergence of resistant Reprints and permissions information is available online at.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/ editorial_policies/license.html#terms * Correspondence and requests for materials should be addressed to C. A. : cameron.alexander@nottingham.ac.uk, Fax: +44 115 951 5102; Tel: +44 115 846 7678 . Author contributionsAll 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. Additional informationSupplementary information is available in the online version of the paper. Competing financial interestsThe authors declare no competing financial interests. Europe PMC Funders GroupAuthor Manuscript Nat Mater. Author manuscript; available in PMC 2015 January 08. Published in final edited form as:Nat Mater. 2014 July ; 13(7): 748-755. doi:10.1038/nmat3949. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts strains of many pathogens is an increasing concern. New approaches to prevent bacterial infections are required that do not invoke the selection of resistant populations. 2 Non-lethal means for targeting bacteria include inactivating their invasive pathways, for example by disrupting cell-cell signalling mechanisms known as Quorum Sensing within microbial populations, [3][4][5] or, more simply, by sequestering bacteria away from an infective site. 6 The latter route is attractive also from a diagnostic perspective, 7 as the binding of a specific orga...

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.

New anti-infective materials are needed urgently as alternatives to conventional biocides. It has recently been established that polymer materials designed to bind to the surface of bacteria can induce the formation of cell clusters which enhance the expression of quorum sensing controlled phenotypes. These materials are relevant for anti-infective strategies as they have the potential to inhibit adhesion while at the same time modulating Quorum Sensing (QS) controlled virulence. Here we carefully evaluate the role that charge and catechol moieties in 2 these polymers play on the binding. We investigate the ability of the cationic polymers poly(N- (5, 7 and 8) and polymer concentration (0.1 and 0.5 mg/mL). We identify that clustering ability is strongly dependent on the balance between charge and hydrophobicity. Moreover, our results suggest that catechol moieties have a positive effect on adhesive properties, but only in the presence of cationic residues such as for P2. Overall, our results highlight the subtle interplay between dynamic natural surfaces and synthetic materials, as well as the need to consider synergistic structure-property relationship when designing antimicrobial polymers.

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. The correct image is shown below, and this error has been corrected in the online versions of the Article.