Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviours, including virulence factor secretion and biofilm formation. Quorum sensing relies on the production, release, accumulation and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviours. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviours. We investigate key features of the compounds, linkers and surfaces necessary to appropriately position molecules to interact with cognate receptors and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviours of bacteria on surfaces.
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The authors acknowledge the Novick laboratory for providing S. aureus strains and plasmids. The authors thank N. Wingreen for discussions about heterogeniety, J. Yan for image analysis, B. Wang for discussion and mentoring in S. aureus genetic techniques, B. Bratton for discussions about single-molecule microscopy, I. Pelczer and K. Conover for the NMR measurements and D. Dabbs for help with the FTIR measurement. The authors acknowledge members of the B.L.B., H.A.S. and T.W.M. laboratories for suggestions. This work was supported by NSF grant MCB-1344191 (to B.L.B. and H.A.S.), the Howard Hughes Medical Institute, NIH grant 2R37GM065859 and NSF grant MCB-0948112 (to B.L.B.), NIH grant R01 AI042783 (to T.W.M.) and a STX fellowship (to M.K.K.).
The authors declare no competing financial interests.
Supplementary Figures 1–8; Supplementary Tables 1 and 2; Supplementary Note 1; Supplementary Methods; Supplementary References; colour-blind-friendly versions of Figures 1–5 and Supplementary Figures 1–8. (PDF 6644 kb)
S. aureus Agr quorum sensing is activated by surface attached AIP-I. Time series of merged fluorescence images of the S. Aureus reporter strain in the presence of Surface-PEG10000-triazole-AIP-I (top left), Surface-PEG10000-triazole-AIP-I + 2.5 μM TrAIP-II in solution (top right), Surface-PEG10000-azide (bottom left), and Surface-PEG10000-triazole LinearAIP-I (bottom right). The time interval between each image is 30 min. (AVI 2147 kb)
S. aureus Agr quorum sensing is inhibited by surface attached TrAIP-II. Time series of merged fluorescence images of the S. Aureus reporter strain in the presence of Surface-PEG10000-triazole-TrAIP-II + 30 nM AIP-I in solution (top left), SurfacePEG10000-triazole-TrAIP-II + 1 μM AIP-I in solution (top right), Surface-PEG10000-azide + 30 nM AIP-I in solution (bottom left), and Surface-PEG10000-triazole-Linear-TrAIP-II + 30 nM AIP-I in solution (bottom right). The time interval between each image is 30 min. (AVI 1750 kb)
Wild-type S. aureus responds to surface-attached AIPI and TrAIP-II. Time series of merged fluorescence images of wild-type S. aureus strain in the presence of Surface-PEG10000-azide (top left), SurfacePEG10000-triazole-AIP-I (top right), Surface-PEG10000-triazole-TrAIP-II (bottom left), and Surface-PEG10000-triazole-TrAIP-II + 1 μM AIP-I in solution (bottom right). The time interval between each image is 30 min. (AVI 1920 kb)
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Kim, M., Zhao, A., Wang, A. et al. Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development. Nat Microbiol 2, 17080 (2017). https://doi.org/10.1038/nmicrobiol.2017.80
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