1887

Abstract

is a member of the complex, a group of genetically similar species that inhabit a number of environmental niches, including the lungs of patients with cystic fibrosis (CF). To colonize the lung, this bacterium requires a source of iron to satisfy its nutritional requirements for this important metal. Because of the high potential for damage in lung tissue resulting from oxygen–iron interactions, this metal is sequestered by a number of mechanisms that render it potentially unavailable to invading micro-organisms. Such mechanisms include the intracellular and extracellular presence of the iron-binding protein ferritin. Ferritin has a highly stable macromolecular structure and may contain up to 4500 iron atoms per molecule. To date, there has been no known report of a pathogenic bacterial species that directly utilizes iron sequestered by this macromolecule. To examine the ability of ferritin to support growth of J2315, iron-deficient media were supplemented with different concentrations of ferritin and the growth kinetics characterized over a 40 h period. The results indicated that J2315 utilizes iron bound by ferritin. Further studies examining the mechanisms of iron uptake from ferritin indicated that iron utilization results from a proteolytic degradation of this otherwise stable macromolecular structure. Since it is known that the ferritin concentration is significantly higher in the CF lung than in healthy lungs, this novel iron-acquisition mechanism may contribute to infection by in people with CF.

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2006-06-01
2019-10-23
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References

  1. Bateman, A., Coin, L., Durbin, R. & 10 other authors ( 2004; ). The Pfam protein families database. Nucleic Acids Res 32, D138–D141.[CrossRef]
    [Google Scholar]
  2. Burkholder, W. H. ( 1950; ). Sour skin, a bacterial rot of onion bulbs. Phytopathology 14, 127–130.
    [Google Scholar]
  3. Crichton, R. R. ( 1969; ). Studies on the structure of ferritin and apoferritin from horse spleen. I. Tryptic digestion of ferritin and apoferritin. Biochim Biophys Acta 194, 34–42.[CrossRef]
    [Google Scholar]
  4. Darling, P., Chan, M., Cox, A. D. & Sokol, P. A. ( 1998; ). Siderophore production by cystic fibrosis isolates of Burkholderia cepacia. Infect Immun 66, 874–877.
    [Google Scholar]
  5. Govan, J. R., Brown, P. H., Maddison, J., Doherty, C. J., Nelson, J. W., Dodd, M., Greening, A. P. & Webb, A. K. ( 1993; ). Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 342, 15–19.[CrossRef]
    [Google Scholar]
  6. Gutteridge, J. M., Quinlan, G. J. & Evans, T. W. ( 2001; ). The iron paradox of heart and lungs and its implications for acute lung injury. Free Radic Res 34, 439–443.[CrossRef]
    [Google Scholar]
  7. Hutchison, M. L., Poxton, I. R. & Govan, J. R. ( 1998; ). Burkholderia cepacia produces a hemolysin that is capable of inducing apoptosis and degranulation of mammalian phagocytes. Infect Immun 66, 2033–2039.
    [Google Scholar]
  8. Isles, A., Maclusky, I., Corey, M., Gold, R., Prober, C., Fleming, P. & Levison, H. ( 1984; ). Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr 104, 206–210.[CrossRef]
    [Google Scholar]
  9. Jin, H., Ren, Z., Whitby, P. W., Morton, D. J. & Stull, T. L. ( 1999; ). Characterization of hgpA, a gene encoding a hemoglobin/hemoglobin-haptoglobin binding protein of Haemophilus influenzae. Microbiology 145, 905–914.[CrossRef]
    [Google Scholar]
  10. Johnson, W. M., Tyler, S. D. & Rozee, K. R. ( 1994; ). Linkage analysis of geographic and clinical clusters in Pseudomonas cepacia infections by multilocus enzyme electrophoresis and ribotyping. J Clin Microbiol 32, 924–930.
    [Google Scholar]
  11. Kooi, C., Cox, A., Darling, P. & Sokol, P. A. ( 1994; ). Neutralizing monoclonal antibodies to an extracellular Pseudomonas cepacia protease. Infect Immun 62, 2811–2817.
    [Google Scholar]
  12. Larson, J. A., Howie, H. L. & So, M. ( 2004; ). Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source. Mol Microbiol 53, 807–820.[CrossRef]
    [Google Scholar]
  13. Lewin, C., Doherty, C. & Govan, J. R. W. ( 1993; ). In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, cotrimoxazole, and ciprofloxacin against Pseudomonas cepacia. Antimicrob Agents Chemother 37, 123–125.[CrossRef]
    [Google Scholar]
  14. Liu, X. & Theil, E. C. ( 2005; ). Ferritins: dynamic management of biological iron and oxygen chemistry. Acc Chem Res 38, 167–175.[CrossRef]
    [Google Scholar]
  15. Mahenthiralingam, E., Urban, T. A. & Goldberg, J. B. ( 2005; ). The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3, 144–156.[CrossRef]
    [Google Scholar]
  16. Morton, D. J. & Stull, T. L. ( 2004; ). Haemophilus. In Iron Transport in Bacteria, pp. 273–292. Edited by J. H. Crosa, A. R. Mey & S. M. Payne. Washington, DC: American Society for Microbiology.
  17. Morton, D. J. & Williams, P. ( 1989; ). Utilization of transferrin-bound iron by Haemophilus species of human and porcine origins. FEMS Microbiol Lett 53, 123–127.
    [Google Scholar]
  18. Morton, D. J., Smith, A., Madore, L. L., VanWagoner, T. M., Seale, T. W., Whitby, P. W. & Stull, T. L. ( 2004; ). Identification of a haem utilization protein (Hup) in Haemophilus influenzae. Microbiology 150, 3923–3933.[CrossRef]
    [Google Scholar]
  19. Nakazawa, T., Yamada, Y. & Ishibashi, M. ( 1987; ). Characterization of hemolysin in extracellular products of Pseudomonas cepacia. J Clin Microbiol 25, 195–198.
    [Google Scholar]
  20. Pitt, T. L., Kaufmann, M. E., Patel, P. S., Benge, L. C., Gaskin, S. & Livermore, D. M. ( 1996; ). Type characterisation and antibiotic susceptibility of Burkholderia (Pseudomonas) cepacia isolates from patients with cystic fibrosis in the United Kingdom and the Republic of Ireland. J Med Microbiol 44, 203–210.[CrossRef]
    [Google Scholar]
  21. Poje, G. & Redfield, R. J. ( 2003; ). General methods for culturing Haemophilus influenzae. Methods Mol Med 71, 51–56.
    [Google Scholar]
  22. Prince, A. ( 1986; ). Antibiotic resistance of Pseudomonas species. J Pediatr 108, 830–834.[CrossRef]
    [Google Scholar]
  23. 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]
  24. Rogers, H. J. ( 1973; ). Iron-binding catechols and virulence in Escherichia coli. Infect Immun 7, 445–456.
    [Google Scholar]
  25. Rosenstein, B. J. & Hall, D. E. ( 1980; ). Pneumonia and septicemia due to Pseudomonas cepacia in a patient with cystic fibrosis. Johns Hopkins Med J 147, 188–189.
    [Google Scholar]
  26. Simpson, I. N., Finlay, J., Winstanley, D. J., Dewhurst, N., Nelson, J. W., Butler, S. L. & Govan, J. R. W. ( 1994; ). Multi-resistance isolates possessing characteristics of both Burkholderia (Pseudomonas) cepacia and Burkholderia gladioli from patients with cystic fibrosis. J Antimicrob Chemother 34, 353–361.[CrossRef]
    [Google Scholar]
  27. Smith, E. L., Markland, F. S., Kasper, C. B., DeLange, R. J., Landon, M. & Evans, W. H. ( 1966; ). The complete amino acid sequence of two types of subtilisin, BPN′ and Carlsberg. J Biol Chem 241, 5974–5976.
    [Google Scholar]
  28. Sokol, P. A. ( 1986; ). Production and utilization of pyochelin by clinical isolates of Pseudomonas cepacia. J Clin Microbiol 23, 560–562.
    [Google Scholar]
  29. 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]
  30. Stites, S. W., Plautz, M. W., Bailey, K., O'Brien-Ladner, A. R. & Wesselius, L. J. ( 1999; ). Increased concentrations of iron and isoferritins in the lower respiratory tract of patients with stable cystic fibrosis. Am J Respir Crit Care Med 160, 796–801.[CrossRef]
    [Google Scholar]
  31. Stull, T. L. ( 1987; ). Protein sources of heme for Haemophilus influenzae. Infect Immun 55, 148–153.
    [Google Scholar]
  32. Thomassen, M. J., Demko, C. A., Klinger, J. D. & Stern, R. C. ( 1985; ). Pseudomonas cepacia colonization among patients with cystic fibrosis. A new opportunist. Am Rev Respir Dis 131, 791–796.
    [Google Scholar]
  33. Turi, J. L., Yang, F., Garrick, M. D., Piantadosi, C. A. & Ghio, A. J. ( 2004; ). The iron cycle and oxidative stress in the lung. Free Radic Biol Med 36, 850–857.[CrossRef]
    [Google Scholar]
  34. Vonberg, R. P. & Gastmeier, P. ( 2005; ). Isolation of infectious cystic fibrosis patients: results of a systematic review. Infect Control Hosp Epidemiol 26, 401–409.[CrossRef]
    [Google Scholar]
  35. Walters, S. & Smith, E. G. ( 1993; ). Pseudomonas cepacia in cystic fibrosis: transmissibility and implications. Lancet 342, 3–4.
    [Google Scholar]
  36. Whitby, P. W., VanWagoner, T. M., Taylor, A. A., Seale, T. W., Morton, D. J., LiPuma, J. J. & Stull, T. L. ( 2006; ). Identification of an RTX determinant of Burkholderia cenocepacia J2315 by subtractive hybridization. J Med Microbiol 55, 11–21.[CrossRef]
    [Google Scholar]
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