1887

Abstract

The success of in cystic fibrosis (CF) and other chronic infections is largely attributed to its ability to grow in antibiotic-resistant biofilm communities. This study investigated the effects of limiting iron levels as a strategy for preventing/disrupting biofilms. A range of synthetic and naturally occurring iron-chelating agents were examined. Biofilm development by strain PAO1 and CF sputum isolates from chronically infected individuals was significantly decreased by iron removal under aerobic atmospheres. CF strains formed poor biofilms under anaerobic conditions. Strain PAO1 was also tested under anaerobic conditions. Biofilm formation by this model strain was almost totally prevented by several of the chelators tested. The ability of synthetic chelators to impair biofilm formation could be reversed by iron addition to cultures, providing evidence that these effective chelating compounds functioned by directly reducing availability of iron to . In contrast, the biological chelator lactoferrin demonstrated enhanced anti-biofilm effects as iron supplementation increased. Hence biofilm inhibition by lactoferrin appeared to occur through more complex mechanisms to those of the synthetic chelators. Overall, our results demonstrate the importance of iron availability to biofilms and that iron chelators have potential as adjunct therapies for preventing biofilm development, especially under low oxygen conditions such as encountered in the chronically infected CF lung.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.004416-0
2009-06-01
2024-12-07
Loading full text...

Full text loading...

/deliver/fulltext/jmm/58/6/765.html?itemId=/content/journal/jmm/10.1099/jmm.0.004416-0&mimeType=html&fmt=ahah

References

  1. Banin E., Brady K. M., Greenberg E. P. 2006; Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm. Appl Environ Microbiol 72:2064–2069 [CrossRef]
    [Google Scholar]
  2. Brock J. H., Liceaga J., Kontoghiorghes G. J. 1988; The effect of synthetic iron chelators on bacterial growth in human serum. FEMS Microbiol Immunol 1:55–60
    [Google Scholar]
  3. Ceri H., Olson M. E., Stremick C., Read R. R., Morick D., Buret A. 1999; The Calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol 37:1771–1776
    [Google Scholar]
  4. Costerton J. W. 2002; Anaerobic biofilm infections in cystic fibrosis. Mol Cell 10:699–700 [CrossRef]
    [Google Scholar]
  5. Heydorn A., Nielsen A. T., Hentzer M., Sternberg C., Givskov M., Ersboll B. K., Molin S. 2000; Quantification of biofilm structures by the novel computer program comstat. Microbiology 146:2395–2407
    [Google Scholar]
  6. Holloway B. W. 1955; Genetic recombination in Pseudomonas aeruginosa . J Gen Microbiol 13:572–581 [CrossRef]
    [Google Scholar]
  7. Kaneko Y., Thoendel M., Olakanmi O., Britigan B. E., Singh P. K. 2007; The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J Clin Invest 117:877–888 [CrossRef]
    [Google Scholar]
  8. Kirov S. M., Webb J. S., O'May C. Y., Reid D. W., Woo J. K., Rice S. A., Kjelleberg S. 2007; Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Microbiology 153:3264–3274 [CrossRef]
    [Google Scholar]
  9. Liu Z. D., Hider R. C. 2002; Design of clinically useful iron(III)-selective chelators. Med Res Rev 22:26–64 [CrossRef]
    [Google Scholar]
  10. Lyczak J. B., Cannon C. L., Pier G. B. 2002; Lung infections associated with cystic fibrosis. Clin Microbiol Rev 15:194–222 [CrossRef]
    [Google Scholar]
  11. Meyer J. M., Abdallah M. A. 1978; The fluorescent pigment of Pseudomonas fluorescens: biosynthesis, purification and physiochemical properties. J Gen Microbiol 107:319–328 [CrossRef]
    [Google Scholar]
  12. Miller J. 1972 Experiments in Molecular Genetics Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  13. Moreau-Marquis S., Bomberger J. M., Anderson G. G., Swiatecka-Urban A., Ye S., O'Toole G. A., Stanton B. A. 2008; The DeltaF508-CFTR mutation results in increased biofilm formation by Pseudomonas aeruginosa by increasing iron availability. Am J Physiol Lung Cell Mol Physiol 295:L25–L37 [CrossRef]
    [Google Scholar]
  14. Musk D. J. Jr, Hergenrother P. J. 2008; Chelated iron sources are inhibitors of Pseudomonas aeruginosa biofilms and distribute efficiently in an in vitro model of drug delivery to the human lung. J Appl Microbiol 105:380–388 [CrossRef]
    [Google Scholar]
  15. Musk D. J., Banko D. A., Hergenrother P. J. 2005; Iron salts perturb biofilm formation and disrupt existing biofilms of Pseudomonas aeruginosa . Chem Biol 12:789–796 [CrossRef]
    [Google Scholar]
  16. Nealson K. H., Saffarini D. 1994; Iron and manganese in anaerobic respiration: environmental significance, physiology, and regulation. Annu Rev Microbiol 48:311–343 [CrossRef]
    [Google Scholar]
  17. O'May C. Y., Reid D. W., Kirov S. M. 2006; Anaerobic culture conditions favor biofilm-like phenotypes in Pseudomonas aeruginosa isolates from patients with cystic fibrosis. FEMS Immunol Med Microbiol 48:373–380 [CrossRef]
    [Google Scholar]
  18. O'Toole G. A., Pratt L. A., Watnick P. I., Newman D. K., Weaver V. B., Kolter R. 1999; Genetic approaches to study of biofilms. Methods Enzymol 310:91–109
    [Google Scholar]
  19. Patriquin G. M., Banin E., Gilmour C., Tuchman R., Greenberg E. P., Poole K. 2008; Influence of quorum sensing and iron on twitching motility and biofilm formation in Pseudomonas aeruginosa . J Bacteriol 190:662–671 [CrossRef]
    [Google Scholar]
  20. Reid D. W., Lam Q. T., Schneider H., Walters E. H. 2004; Airway iron and iron-regulatory cytokines in cystic fibrosis. Eur Respir J 24:286–291 [CrossRef]
    [Google Scholar]
  21. Reid D. W., Carroll V., O'May C., Champion A., Kirov S. M. 2007; Increased airway iron as a potential factor in the persistence of Pseudomonas aeruginosa infection in cystic fibrosis. Eur Respir J 30:286–292 [CrossRef]
    [Google Scholar]
  22. Singh P. K., Schaefer A. L., Parsek M. R., Moninger T. O., Welsh M. J., Greenberg E. P. 2000; Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407:762–764 [CrossRef]
    [Google Scholar]
  23. Singh P. K., Parsek M. R., Greenberg E. P., Welsh M. J. 2002; A component of innate immunity prevents bacterial biofilm development. Nature 417:552–555 [CrossRef]
    [Google Scholar]
  24. Stewart P. S., Franklin M. J. 2008; Physiological heterogeneity in biofilms. Nat Rev Microbiol 6:199–210 [CrossRef]
    [Google Scholar]
  25. Stites S. W., Walters B., O'Brien-Ladner A. R., Bailey K., Wesselius L. J. 1998; Increased iron and ferritin content of sputum from patients with cystic fibrosis or chronic bronchitis. Chest 114:814–819 [CrossRef]
    [Google Scholar]
  26. Takase H., Nitanai H., Hoshino K., Otani T. 2000; Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice. Infect Immun 68:1834–1839 [CrossRef]
    [Google Scholar]
  27. Vasil M. L. 2007; How we learnt about iron acquisition in Pseudomonas aeruginosa : a series of very fortunate events. Biometals 20:587–601 [CrossRef]
    [Google Scholar]
  28. Vasil M. L., Ochsner A. 1999; The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Mol Microbiol 34:399–413 [CrossRef]
    [Google Scholar]
  29. Webb J. S., Thompson L. S., James S., Charlton T., Tolker-Nielsen T., Koch B., Givskov M., Kjelleberg S. 2003; Cell death in Pseudomonas aeruginosa biofilm development. J Bacteriol 185:4585–4592 [CrossRef]
    [Google Scholar]
  30. Weinberg E. D. 2004; Suppression of bacterial biofilm formation by iron limitation. Med Hypotheses 63:863–865 [CrossRef]
    [Google Scholar]
  31. Worlitzsch D., Tarran R., Ulrich M., Schwab U., Cekici A., Meyer K. C., Birrer P., Bellon G., Berger J. other authors 2002; Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest 109:317–325 [CrossRef]
    [Google Scholar]
  32. Yang L., Barken K. B., Skindersoe M. E., Christensen A. B., Givskov M., Tolker-Nielsen T. 2007; Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa . Microbiology 153:1318–1328 [CrossRef]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.004416-0
Loading
/content/journal/jmm/10.1099/jmm.0.004416-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error