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Dynamic biofilm architecture confers individual and collective mechanisms of viral protection


In nature, bacteria primarily live in surface-attached, multicellular communities, termed biofilms1,2,3,4,5,6. In medical settings, biofilms cause devastating damage during chronic and acute infections; indeed, bacteria are often viewed as agents of human disease7. However, bacteria themselves suffer from diseases, most notably in the form of viral pathogens termed bacteriophages8,9,10,11,12, which are the most abundant replicating entities on Earth. Phage–biofilm encounters are undoubtedly common in the environment, but the mechanisms that determine the outcome of these encounters are unknown. Using Escherichia coli biofilms and the lytic phage T7 as models, we discovered that an amyloid fibre network of CsgA (curli polymer) protects biofilms against phage attack via two separate mechanisms. First, collective cell protection results from inhibition of phage transport into the biofilm, which we demonstrate in vivo and in vitro. Second, CsgA fibres protect cells individually by coating their surface and binding phage particles, thereby preventing their attachment to the cell exterior. These insights into biofilm–phage interactions have broad-ranging implications for the design of phage applications in biotechnology, phage therapy and the evolutionary dynamics of phages with their bacterial hosts.

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Fig. 1: Susceptibility of biofilms to phage exposure as a function of biofilm age.
Fig. 2: Phage susceptibility of biofilms depends on extracellular matrix structure and dynamics.
Fig. 3: Phage localization and biofilm architectural properties within wild-type E. coli and mutants lacking major extracellular matrix components.
Fig. 4: Reconstruction of minimal synthetic biofilms recapitulates phage diffusion prevention and phage–cell attachment prevention in vivo.


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The authors thank M. Rakwalska-Bange, T. Heimerl and G. Malengo for experimental assistance, R. Hengge and V. Sourjik for strains and N. Rigel and members of the Drescher laboratory for discussions and suggestions. This work was supported by grants from the Max Planck Society, Behrens Weise Foundation, European Research Council (StG-716734), Human Frontier Science Program (CDA00084/2015-C) and Deutsche Forschungsgemeinschaft (SFB987) to K.D., and the Alexander von Humboldt Foundation and Cystic Fibrosis Foundation (STANTO15RO) to C.D.N.

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C.D.N. conceived the topic. C.D.N. and K.D. designed the project. L.V. and P.K.S. generated strains and acquired data. R.H. developed new analytical software. L.V., R.H., C.D.N. and K.D. analysed and interpreted the data. L.V., C.D.N. and K.D. wrote the paper with the help of all authors.

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Correspondence to Carey D. Nadell or Knut Drescher.

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Supplementary Figures 1–10, Supplementary Table 1, Supplementary References.

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Vidakovic, L., Singh, P.K., Hartmann, R. et al. Dynamic biofilm architecture confers individual and collective mechanisms of viral protection. Nat Microbiol 3, 26–31 (2018).

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