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A component of innate immunity prevents bacterial biofilm development

Nature volume 417, pages 552–555 (2002)Cite this article

Abstract

Antimicrobial factors form one arm of the innate immune system, which protects mucosal surfaces from bacterial infection1,2,3. These factors can rapidly kill bacteria deposited on mucosal surfaces and prevent acute invasive infections1,2,3,4. In many chronic infections, however, bacteria live in biofilms, which are distinct, matrix-encased communities specialized for surface persistence5,6,7. The transition from a free-living, independent existence to a biofilm lifestyle can be devastating, because biofilms notoriously resist killing by host defence mechanisms and antibiotics5,8. We hypothesized that the innate immune system possesses specific activity to protect against biofilm infections. Here we show that lactoferrin, a ubiquitous and abundant constituent of human external secretions, blocks biofilm development by the opportunistic pathogen Pseudomonas aeruginosa. This occurs at lactoferrin concentrations below those that kill or prevent growth. By chelating iron, lactoferrin stimulates twitching, a specialized form of surface motility, causing the bacteria to wander across the surface instead of forming cell clusters and biofilms. These findings reveal a specific anti-biofilm defence mechanism acting at a critical juncture in biofilm development, the time bacteria stop roaming as individuals and aggregate into durable communities.

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Figure 1: Growth of P. aeruginosa in the presence of lactoferrin.
Figure 2: Confocal microscopic images of GFP-labelled P. aeruginosa in biofilm flow cells perfused with lactoferrin-free (a–d) and lactoferrin-containing (20 µg ml-1) (e–h) media.
Figure 3: Representations of bacterial behaviours.
Figure 4: Role of iron in twitching motility and biofilm development.
Figure 5: Effect of conalbumin on the antimicrobial susceptibility of P. aeruginosa biofilms to tobramycin (a) and H2O2 (b).

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Acknowledgements

We thank E. Brutinel, T. Moninger and M. Neville for technical assistance, J. Kato of Hiroshima University for the twitching mutant, A. Berger for advice on data analysis, and our laboratory colleagues for discussions. This research was supported by the Howard Hughes Medical Institute, the National Heart, Lung and Blood Institute, the National Institute of General Medical Science, the Cystic Fibrosis Foundation, and the W. M. Keck Foundation Microbial Communities and Cell Signaling Laboratory. P.K.S. is the recipient of a NIH Mentored Physician Scientist Award, and a Cystic Fibrosis Foundation Leroy Matthews Award. M.J.W. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    Pradeep K. Singh & Michael J. Welsh

  2. Department of Microbiology, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    E. Peter Greenberg

  3. Department of Physiology and Biophysics and Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA

    Michael J. Welsh

  4. Department of Civil Engineering, Northwestern University, Evanston, Illinois, 60208, USA

    Matthew R. Parsek

  5. W. M. Keck Foundation Microbial Communities and Cell Signaling Laboratory, Iowa City, Iowa, 52242, USA

    E. Peter Greenberg & Michael J. Welsh

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Correspondence to Pradeep K. Singh.

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Singh, P., Parsek, M., Greenberg, E. et al. A component of innate immunity prevents bacterial biofilm development. Nature 417, 552–555 (2002). https://doi.org/10.1038/417552a

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