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Mucins trigger dispersal of Pseudomonas aeruginosa biofilms

Co, Julia Y., Cárcamo-Oyarce, Gerardo, Billings, Nicole, Wheeler, Kelsey M., Grindy, Scott C., Holten-Andersen, Niels, Ribbeck, Katharina·2018·npj Biofilms and Microbiomes
DOI 10.1038/s41522-018-0067-0
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Abstract

Mucus is a biological gel that lines all wet epithelia in the body, including the mouth, lungs, and digestive tract, and has evolved to protect the body from pathogenic infection. However, microbial pathogenesis is often studied in mucus-free environments that lack the geometric constraints and microbial interactions in physiological three-dimensional mucus gels. We developed fluid-flow and static test systems based on purified mucin polymers, the major gel-forming constituents of the mucus barrier, to understand how the mucus barrier influences bacterial virulence, particularly the integrity of Pseudomonas aeruginosa biofilms, which can become resistant to immune clearance and antimicrobial agents. We found that mucins separate the cells in P. aeruginosa biofilms and disperse them into suspension. Other viscous polymer solutions did not match the biofilm disruption caused by mucins, suggesting that mucin-specific properties mediate the phenomenon. Cellular dispersion depended on functional flagella, indicating a role for swimming motility. Taken together, our observations support a model in which host mucins are key players in the regulation of microbial virulence. These mucins should be considered in studies of mucosal pathogenesis and during the development of novel strategies to treat biofilms.

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Research works printed but not linked: 58

  1. O’Toole, G., Kaplan, H. B. & Kolter, R. Biofilm formation as microbial development. Annu. Rev. Microbiol. 54, 49–79 (2000). · DOI · Paper page
  2. Hall-Stoodley, L., Costerton, J. W. & Stoodley, P. Bacterial biofilms: from the natural environment to infectious diseases. Nat. Rev. Microbiol. 2, 95–108 (2004). · DOI · Paper page
  3. Flemming, H. C., Neu, T. R. & Wozniak, D. J. The EPS matrix: the ‘house of biofilm cells’. J. Bacteriol. 189, 7945–7947 (2007). · DOI · Paper page
  4. Darouiche, R. O. Device-associated infections: a macroproblem that starts with microadherence. Clin. Infect. Dis. 33, 1567–1572 (2001). · DOI · Paper page
  5. Wozniak, D. J. et al. Alginate is not a significant component of the extracellular polysaccharide matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms. Proc. Natl. Acad. Sci. U.S.A. 100, 7907–7912 (2003). · DOI · Paper page
  6. Hall-Stoodley, L. & Stoodley, P. Biofilm formation and dispersal and the transmission of human pathogens. Trends Microbiol. 13, 7–10 (2005). · DOI · Paper page
  7. Johansson, M. E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl. Acad. Sci. U.S.A. 105, 15064–15069 (2008). · DOI · Paper page
  8. Linden, S. K., Sutton, P., Karlsson, N. G., Korolik, V. & McGuckin, M. A. Mucins in the mucosal barrier to infection. Mucosal Immunol. 1, 183–197 (2008). · DOI · Paper page
  9. Bansil, R. & Turner, B. S. Mucin structure, aggregation, physiological functions and biomedical applications. Curr. Opin. Colloid Interface Sci. 11, 164–170 (2006). · DOI · Paper page
  10. Hattrup, C. L. & Gendler, S. J. Structure and function of the cell surface (tethered) mucins. Annu. Rev. Physiol. 70, 431–457 (2008). · DOI · Paper page
  11. Rose, M. C. & Voynow, J. A. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol. Rev. 86, 245–278 (2006). · DOI · Paper page
  12. Henke, M. O., John, G., Germann, M., Lindemann, H. & Rubin, B. K. MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation. Am. J. Respir. Crit. Care Med. 175, 816–821 (2007). · DOI
  13. Caramori, G. et al. Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease. Histopathology 45, 477–484 (2004). · DOI · Paper page
  14. Van der Sluis, M. et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117–129 (2006). · DOI · Paper page
  15. Tilley, A. E., Walters, M. S., Shaykhiev, R. & Crystal, R. G. Cilia dysfunction in lung disease. Annu. Rev. Physiol. 77, 379–406 (2015). · DOI · Paper page
  16. Zemanick, E. T. & Hoffman, L. R. Cystic fibrosis: microbiology and host response. Pediatr. Clin. North Am. 63, 617–636 (2016). · DOI
  17. Kavanaugh, N. L., Zhang, A. Q., Nobile, C. J., Johnson, A. D. & Ribbeck, K. Mucins suppress virulence traits of Candida albicans. mBio 5, e01911 (2014). · DOI
  18. Caldara, M. et al. Mucin biopolymers prevent bacterial aggregation by retaining cells in the free-swimming state. Curr. Biol. 22, 2325–2330 (2012). · DOI
  19. Celli, J. P. et al. Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proc. Natl. Acad. Sci. U.S.A. 106, 14321–14326 (2009). · DOI · Paper page
  20. Stewart, P. S. & Costerton, J. W. Antibiotic resistance of bacteria in biofilms. Lancet 358, 135–138 (2001). · DOI · Paper page
  21. Høiby, N., Bjarnsholt, T., Givskov, M., Molin, S. & Ciofu, O. Antibiotic resistance of bacterial biofilms. Int. J. Antimicrob. Agents 35, 322–332 (2010). · DOI · Paper page
  22. Bjarnsholt, T. et al. The in vivo biofilm. Trends Microbiol. 21, 466–474 (2013). · DOI · Paper page
  23. Kocevar-Nared, J., Kristl, J. & Smid-Korbar, J. Comparative rheological investigation of crude gastric mucin and natural gastric mucus. Biomaterials 18, 677–681 (1997). · DOI · Paper page
  24. Crater, J. S. & Carrier, R. L. Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol. Biosci. 10, 1473–1483 (2010). · DOI · Paper page
  25. Billings, N., Rusconi, R., Stocker, R. & Ribbeck, K. Microfluidic-based time-kill kinetic assay. Bio-Protocol 4, e1116 (2014).
  26. Wanner, O., Cunningham, A. B. & Lundman, R. Modeling biofilm accumulation and mass transport in a porous medium under high substrate loading. Biotechnol. Bioeng. 47, 703–712 (1995). · doi:10.1002/bit.260470611
  27. Stoodley, P., Lewandowski, Z., Boyle, J. D. & Lappin-Scott, H. M. Structural deformation of bacterial biofilms caused by short-term fluctuations in fluid shear: an in situ investigation of biofilm rheology. Biotechnol. Bioeng. 65, 83–92 (1999). · DOI · Paper page
  28. Stoodley, P. et al. Growth and detachment of cell clusters from mature mixed-species biofilms. Appl. Environ. Microbiol. 67, 5608–5613 (2001). · DOI · Paper page
  29. Thornton, D. J. & Sheehan, J. K. From mucins to mucus: toward a more coherent understanding of this essential barrier. Proc. Am. Thorac. Soc. 1, 54–61 (2004). · DOI · Paper page
  30. Worku, M. L. et al. Motility of Helicobacter pylori in a viscous environment. Eur. J. Gastroenterol. Hepatol. 11, 1143–1150 (1999). · doi:10.1097/00042737-199910000-00012
  31. Smith, D. J., Gaffney, E. A., Gadelha, H., Kapur, N. & Kirkman-Brown, J. C. Bend propagation in the flagella of migrating human sperm, and its modulation by viscosity. Cell Motil. Cytoskelet. 66, 220–236 (2009). · DOI · Paper page
  32. Banerjee, I., Pangule, R. C. & Kane, R. S. Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv. Mater. 23, 690–718 (2011). · DOI · Paper page
  33. Arora, S. K., Ritchings, B. W., Almira, E. C., Lory, S. & Ramphal, R. The Pseudomonas aeruginosa flagellar cap protein, FliD, is responsible for mucin adhesion. Infect. Immun. 66, 1000–1007 (1998). · DOI · Paper page
  34. Scharfman, A. et al. Recognition of Lewis x derivatives present on mucins by flagellar components of Pseudomonas aeruginosa. Infect. Immun. 69, 5243–5248 (2001). · DOI
  35. Landry, R. M., An, D., Hupp, J. T., Singh, P. K. & Parsek, M. R. Mucin–Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance. Mol. Microbiol. 59, 142–151 (2006). · DOI · Paper page
  36. Davies, D. G. Biofilm dispersion. In Biofilm Highlights (eds. Flemming, H.-C., Wingender, J. & Szewzyk, U.) Vol. 5, 1–28 (Springer, Berlin, Heidelberg, 2011). · DOI
  37. Toutain, C. M., Zegans, M. E. & O’Toole, G. A. Evidence for two flagellar stators and their role in the motility of Pseudomonas aeruginosa. J. Bacteriol. 187, 771–777 (2005). · DOI · Paper page
  38. Smith, B. F. & LaMont, J. T. Hydrophobic binding properties of bovine gallbladder mucin. J. Biol. Chem. 259, 12170–12177 (1984). · DOI
  39. Gong, D. H., Turner, B., Bhaskar, K. R. & Lamont, J. T. Lipid binding to gastric mucin: protective effect against oxygen radicals. Am. J. Physiol. 259, G681–G686 (1990).
  40. Chua, S. L. et al. Dispersed cells represent a distinct stage in the transition from bacterial biofilm to planktonic lifestyles. Nat. Commun. 5, 4462 (2014). · DOI · Paper page
  41. Petrova, O. E. & Sauer, K. Escaping the biofilm in more than one way: desorption, detachment or dispersion. Curr. Opin. Microbiol. 30, 67–78 (2016). · DOI · Paper page
  42. Johansson, E. M. et al. Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB. Chem. Biol. 15, 1249–1257 (2008). · DOI · Paper page
  43. Karwacki, M. T. et al. Antibiofilm activity of Actinobacillus pleuropneumoniae serotype 5 capsular polysaccharide. PLoS One 8, e63844 (2013). · DOI
  44. Murugan, K., Selvanayaki, K. & Al-Sohaibani, S. Urinary catheter indwelling clinical pathogen biofilm formation, exopolysaccharide characterization and their growth influencing parameters. Saudi J. Biol. Sci. 23, 150–159 (2016). · DOI
  45. Wu, S., Liu, G., Jin, W., Xiu, P. & Sun, C. Antibiofilm and anti-Infection of a marine bacterial exopolysaccharide against Pseudomonas aeruginosa. Front. Microbiol. 7, 102 (2016).
  46. Simpson, D. A., Ramphal, R. & Lory, S. Genetic analysis of Pseudomonas aeruginosa adherence: distinct genetic loci control attachment to epithelial cells and mucins. Infect. Immun. 60, 3771–3779 (1992). · DOI
  47. Arora, S. K., Ritchings, B. W., Almira, E. C., Lory, S. & Ramphal, R. Cloning and characterization of Pseudomonas aeruginosa fliF, necessary for flagellar assembly and bacterial adherence to mucin. Infect. Immun. 64, 2130–2136 (1996). · DOI
  48. Tolker-Nielsen, T. & Molin, S. Spatial organization of microbial biofilm communities. Microb. Ecol. 40, 75–84 (2000). · DOI · Paper page
  49. Stewart, P. S. & Franklin, M. J. Physiological heterogeneity in biofilms. Nat. Rev. Microbiol. 6, 199–210 (2008). · DOI · Paper page
  50. Fahy, J. V. & Dickey, B. F. Airway mucus function and dysfunction. N. Engl. J. Med. 363, 2233–2247 (2010). · DOI · Paper page
  51. Adler, K. B., Tuvim, M. J. & Dickey, B. F. Regulated mucin secretion from airway epithelial cells. Front. Endocrinol. 4, 129 (2013). · DOI
  52. Livraghi-Butrico, A. et al. Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol. 10, 395–407 (2017). · DOI
  53. Matsui, H. et al. A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms. Proc. Natl. Acad. Sci. U.S.A. 103, 18131–18136 (2006). · DOI · Paper page
  54. Billings, N. et al. The extracellular matrix component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog. 9, e1003526 (2013). · DOI · Paper page
  55. Heydorn, A. et al. Quantification of biofilm structures by the novel computer program COMSTAT. Microbiology 146(Pt 1), 2395–2407 (2000). · DOI · Paper page
  56. Chua, S. L. et al. In vitro and in vivo generation and characterization of Pseudomonas aeruginosa biofilm-dispersed cells via c-di-GMP manipulation. Nat. Protoc. 10, 1165–1180 (2015). · DOI
  57. Heydorn, A. et al. Experimental reproducibility in flow-chamber biofilms. Microbiology 146(Pt 1), 2409–2415 (2000). · DOI · Paper page
  58. Ha, D. G., Kuchma, S. L. & O’Toole, G. A. Plate-based assay for swimming motility in Pseudomonas aeruginosa in. Methods Mol. Biol. 1149, 59–65 (2014). · DOI

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Metadata

Authors
Co, J. Y., Cárcamo-Oyarce, G., Billings, N., Wheeler, K. M., Grindy, S. C., Holten-Andersen, N., & Ribbeck, K.
Venue
npj Biofilms and Microbiomes
Publisher
Springer Science and Business Media LLC
Published
2018-10-10
Volume
4
Issue
1
ISSN
2055-5008
DOI
10.1038/s41522-018-0067-0
Cited by
95
References
9
Language
en
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CoChat. (2026). Citation check: Mucins trigger dispersal of Pseudomonas aeruginosa biofilms. https://app.cochat.ai/papers/10.1038/s41522-018-0067-0
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Co, J. Y., Cárcamo-Oyarce, G., Billings, N., Wheeler, K. M., Grindy, S. C., Holten-Andersen, N., & Ribbeck, K. (2018). Mucins trigger dispersal of Pseudomonas aeruginosa biofilms. npj Biofilms and Microbiomes. https://doi.org/10.1038/s41522-018-0067-0

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