Skip to main content
SpringerLink
Log in

Chronic Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis Patients

  • Chapter
Pseudomonas aeruginosa as an Opportunistic Pathogen

Part of the book series: Infectious Agents and Pathogenesis ((IAPA))

Abstract

Cystic fibrosis (CF) is the most common lethal genetic disease in white populations, affecting approximately 1 in 2000 to 1 in 4000 live births in Europe and North America.1 Fifty-three years after it was first described,2 the gene responsible for the generalized metabolic disorder was identified on chromosome 7.3–5 It is expressed in a variety of tissues that are affected in CF patients, such as the lungs, pancreas, liver, sweat glands, and nasal epithelia. The gene encodes a membrane protein that most probably regulates ion transport and/or is an ion channel itself, and was therefore named “Cystic Fibrosis Transmembrane Conductance Regulator” (CFTR). The major mutation in CFTR, present in about 70% of the CF mutant chromosomes, is the deletion of a single amino acid residue at position 508. The frequency of ΔF508 varies considerably depending on the geographic location; so far, more than 60 mutations in CFTR differing from ΔF508 have been reported from CF patients.6

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Harris, J. H., and Nadler, H. L., 1983, Incidence, genetics, heterozygote, and ante-natal detection of cystic fibrosis, in: Textbook of Cystic Fibrosis, U. D. Lloyd-Still, ed.), John Wright, Boston, pp. 1–7.

    Google Scholar 

  2. Fanconi, G., Uehlinger, E., and Knauer, C., 1936, Das Coeliakiesyndrom bei angeborener zystischer Pankreas-Fibromatose und Bronchiektasen, Wien. Med. Wochensch. 86:753–756.

    Google Scholar 

  3. Rommens, J. M., Iannuzzi, M. C., Kerem, B., Melmer, G., Drumm, M. L., Melmer, G., Dean, M., Rozmahel, R., Cole, J. L., Kennedy, D., Hidaka, N., Zsiga, M., Buchwald, M., Riordan, J. R., Tsui, L.-C., and Collins, E. S., 1989, Identification of the cystic fibrosis gene: Chromosome walking and jumping, Science 245:1059–1065.

    Article  PubMed  CAS  Google Scholar 

  4. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelzak, J., Zielenski, J., Silok, S., Playsic, N., Chou, J.-I.., Drumm, M. L., Iannuzzi, M. C., Collins, E. S., and Tsui, L.-C., 1989, Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA, Science 245:1066–1073.

    Article  PubMed  CAS  Google Scholar 

  5. Kerem, B. Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarty, A., Buchwald,M., and Tsui, L.-C., 1989, Identification of the Scystic fibrosis gene: Genetic analysis,Science 245:1073–1080.

    Article  PubMed  CAS  Google Scholar 

  6. Tsui, L.-C., 1991, Molecular genetics of cystic fibrosis and possible mechanisms of protein function, World Health Organization, Hereditary diseases program, Report of a joint WHO/ ICF(M)A task force on cystic fibrosis, Annex 1, pp. 21–30.

    Google Scholar 

  7. Li, M., McCann, J. D., Liedtke, C. M., Nairn, A. C., Greengard, E, and Welsh, M. J., 1988, Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium, Nature 331:358–360.

    Article  PubMed  CAS  Google Scholar 

  8. Boucher, R. C., Stutts, M. J., Knowles, M. R., Cantley, L., and Gatzy, J. T., 1986, Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation, J. Clin. Invest. 78:1245–1252.

    Article  PubMed  CAS  Google Scholar 

  9. Cheng, P.-W., Boat, F. E., Cranfill, K., Yankaskas, I. R., and Boucher, R. C., 1989, Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis, J. Clin. Invest. 84:68–72.

    Article  PubMed  CAS  Google Scholar 

  10. Lloyd-Still, J. D., 1983, Pulmonary manifestations, in: Textbook of Cystic Fibrosis, (J.D. Lloyd-Still, ed.), John Wright, Boston, pp. 165–198.

    Google Scholar 

  11. Wood, R. E., 1989, Treatment of cystic fibrosis lung disease in the first two years, Pediatr. Pulmonol. Suppl. 4:68–70.

    Google Scholar 

  12. Bellon, G., Chomarat, M., and Döring, G., 1991, Bacterial ecology in the airways of cystic fibrosis patients. Abstr. 17th Annu. Meet. E.W.G.C.F.

    Google Scholar 

  13. Høiby, N., 1982, Microbiology of lung infections in cystic fibrosis patients, Acta Paediatr. Scand. Suppl. 301:33–54.

    Article  Google Scholar 

  14. Myers, M. G., Koontz, E, and Weinberger, M., 1983, Lower respiratory infections in patients with cystic fibrosis, in: Textbook of Cystic Fibrosis, (J. D. Lloyd-Still, ed.), John Wright, Boston, pp. 91–107.

    Google Scholar 

  15. Wood, R. E., Boat, T. E., and Doershuk, C. E., 1976, Cystic fibrosis: state of the art, Am. Rev. Respir. Dis. 113:833–878.

    PubMed  CAS  Google Scholar 

  16. Kulczycki, L. L., Murphy, T. M., and Bellanti, J. A., 1978, Pseudomonas colonization in cystic fibrosis. A study of 160 patients, J.A.M.A. 240:30–34.

    Article  PubMed  CAS  Google Scholar 

  17. diSant’Agnese, P. A., and Davis, P. A., 1976, Research in cystic fibrosis, III, N. Engl. J. Med. 295:597–602.

    Article  Google Scholar 

  18. Lebenthal, E., and Baswell, D., 1983, The pancreas in cystic fibrosis, in: Textbook of Cystic Fibrosis,(J. D. Lloyd-Still, ed.), John Wright, Boston, pp. 293–312.

    Google Scholar 

  19. Jensen, T, Pedersen, S. S., Høby, N., Koch, C., Flensborg, E. W, 1989, Use of antibiotics in cystic fibrosis. The Danish approach, Antibiot. Chemother. 42:237–246.

    PubMed  CAS  Google Scholar 

  20. Krogh-Johansen, H., Nir, M., Høby, N., Koch, C., and Schwartz, M.,1991, Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation, Lancet 337: 631–634.

    Article  Google Scholar 

  21. Döring, G., Ulrich, M., Müller, W, Bitzer, J., Schmidt-Koenig, L., Münst, L., Grupp, H., Wolz, C., Stern, M., and Botzenhart, K., 1991, Generation of Pseudomonas aeruginosa aerosols during handwashing from contaminated sink drains, transmission to hands of hospital personnel, and its prevention by use of a new heating device, Zentralbl. Hyg. 191: 494–505.

    Google Scholar 

  22. Høby, N., and Rosendal, K., 1980, Epidemiology of Pseudomonas aeruginosa infections in cystic fibrosis, Acta Pathol. Microbiol. Scand. Sect [B] 88:125–131.

    Google Scholar 

  23. Kelly, N. M., Falkiner, E R., Tempany, E., Fitzgerald, M. X., O’Boyle, C., and Keane, C. T., 1982, Does Pseudomonas cross-infection occur between cystic fibrosis patients? Lancet ii: 688–690.

    Article  Google Scholar 

  24. Laraya-Cuasay, L. R., Cundy, K. R., and Huang, N. N., 1976, Pseudomonas carrier rates of patients with cystic fibrosis and of members of their families, J. Pediatrics 89:23–26.

    Article  CAS  Google Scholar 

  25. Seale, T. W, Thirkill, H., Tarpay, M., Flux, M., and Rennert, O. M., 1979, Serotypes and antibiotic susceptibilities of Pseudomonas aeruginosa isolates from single sputa of cystic fibrosis patients, J. Clin. Microbiol. 9:72–78.

    PubMed  CAS  Google Scholar 

  26. Speert, D. P., Lawton, D., and Damm, S., 1982, Communicability of Pseudomonas aeruginosa in a cystic fibrosis summer camp, J. Pediatrics 101:227–229.

    Article  CAS  Google Scholar 

  27. Speert, D. P., and Campbell, M. E., 1987, Hospital epidemiology of Pseudomonas aeruginosa from patients with cystic fibrosis, J. Hosp. Infect. 9:11–21.

    Article  PubMed  CAS  Google Scholar 

  28. Thomassen, M. J., Demko, C. A., Doershuk, C. E, and Root, J. M., 1985, Pseudomonas aeruginosa isolates: Comparison of isolates from campers and from sibling pairs with cystic fibrosis, Pediatr. Pulmonol. 1:40–45.

    Article  PubMed  CAS  Google Scholar 

  29. Zierdt, C. H., and Williams, R. L., 1975, Serotyping of Pseudomonas aeruginosa isolates from patients with cystic fibrosis of the pancreas, J. Clin. Microbiol. 1:521–526.

    PubMed  CAS  Google Scholar 

  30. Pedersen, S. S., Koch, C., Høby, N., and Rosendal, K., 1986, An epidemic spread of multiresistant Pseudomonas aeruginosa in a cystic fibrosis center, J. Antimicrob. Chemother. 17: 505–516.

    Article  PubMed  CAS  Google Scholar 

  31. Zimakoff, J., Høby, N., Rosendal, K., and Guilbert, J. R, 1983, Epidemiology of Pseudomonas aeruginosa infection and the role of contamination of the environment in a cystic fibrosis clinic, J. Hosp. Infect. 4:31–40.

    Article  PubMed  CAS  Google Scholar 

  32. Bergan, T, and Høiby, N., 1975, Epidemiological markers for Pseudomonas aeruginosa. 6. Relationship between concomitant nonmucoid and mucoid strains from the respiratory tract in cystic fibrosis, Acta Pathol. Microbiol. Immunol. Scand. [B] 83:553–560.

    CAS  Google Scholar 

  33. Grothus, D., Koopmann, U., von der Hardt, H., and Tümmler, B., 1988, Genome fingerprinting of Pseudomonas aeruginosa indicates colonization of cystic fibrosis siblings with closely related strains, J Clin. Microbiol. 26:1973–1977.

    Google Scholar 

  34. Wolz, C., Kiosz, G., Ogle, J. W, Vasil, M. L., Schaad, U., Botzenhart, K., and Döring, G., 1989, Pseudomonas aeruginosa cross-colonization and persistence in patients with cystic fibrosis. Use of a DNA probe, Epidem. Infect. 102:205–214.

    Article  CAS  Google Scholar 

  35. Tümmler, B., Koopmann, U., Grothus, D., Weissbrodt, H., Steinkamp, G., and von der Hardt, H., 1991, Nosocomial acquisition of Pseudomonas aeruginosa by cystic fibrosis patients, J. Clin. Microbiol. 29:1265–1267.

    PubMed  Google Scholar 

  36. Høiby, N., and Pedersen, S. S., 1989, Cross-infection with Pseudomonas aeruginosa in Danish cystic fibrosis patients, Antibiot. Chemother. 42:124–129.

    PubMed  Google Scholar 

  37. Ogle, J. W., Janda, J. M., Woods, D. E., and Vasil, M. L., 1987, Characterization and use of a DNA probe as an epidemiological marker for Pseudomonas aeruginosa, J. Infect. Dis. 155: 119–126.

    Article  PubMed  CAS  Google Scholar 

  38. Vasil, M. L., Chamberlain, C., and Grant, C., 1986, Molecular studies of Pseudomonas exotoxin A gene, Infect. Immun. 52:538–548.

    PubMed  CAS  Google Scholar 

  39. Ojeniyi, B., Wolz, C., Döring, G., Lam, J. S., Rosdahl, V. T., and Høby, N., 1990, Typing of polyagglutinable Pseudomonas aeruginosa isolates from cystic fibrosis patients, Acta Pathol. Microbiol. Immunol. Scand. 98:423–431.

    CAS  Google Scholar 

  40. Ojeniyi, B., and Høby, N., 1991, Comparison of different typing methods of Pseudomonas aeruginosa, Antibiot. Chemother. 44:13–22.

    PubMed  CAS  Google Scholar 

  41. Döring, G., Bareth, H., Gairing, A., Wolz, C., and Botzenhart, K., 1989, Genotyping of Pseudomonas aeruginosa sputum and stool isolates from cystic fibrosis patients: Evidence for intestinal colonization and spreading into toilets, Epidem. Infect. 103:555–564.

    Article  Google Scholar 

  42. Remington, J. S., and Schimpff, S. C., 1981, Please don’t eat the salads, N. Engl. J. Med. 304: 433–435.

    Article  PubMed  CAS  Google Scholar 

  43. Gerba, C. P., Wallis, C., and Melnick, J. L., 1975, Microbial hazards of household toilets: Droplet production and the fate of residual organisms, Appl. Microbiol. 30:229–237.

    PubMed  CAS  Google Scholar 

  44. Darlow, H. M., and Bale, W. R., 1959, Infective hazards of water-closets, Lancet 1:1196–1200.

    Article  PubMed  CAS  Google Scholar 

  45. Exner, M., Vogel, E, and Stelzner, M., 1982, Occurrence of Pseudomonas aeruginosa in the oropharynx, Hyg. Med. 7:550–552.

    Google Scholar 

  46. Levison, M. E., 1977, Factors influencing colonization of the gastrointestinal tract with Pseudomonas aeruginosa, in: Pseudomonas aeruginosa: Ecological Aspects and Patient Colonization, (V. M. Young, ed.), Raven Press, New York, pp. 97–109.

    Google Scholar 

  47. Hentges, D.J., Stein, A. J., Casey, S. W., and Que, J. U., 1985, Protective role of intestinal flora against infection with Pseudomonas aeruginosa in mice: Influence of antibiotics on colonization resistance, Infect. Immun. 47:118–122.

    PubMed  CAS  Google Scholar 

  48. Lloyd-Still, J. D., 1983, Growth, nutrition and gastrointestinal problems, in: Textbook of cystic fibrosis,Q. D. Lloyd-Still, ed.), John Wright, Bristol, pp. 223–267.

    Google Scholar 

  49. Vander Wauven, C., Piérard, A., Kley-Raymann, M., and Haas, D., 1984, Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: Evidence for a four gene cluster encoding the arginine deiminase pathway, J. Bacteriol. 160:928–934.

    Google Scholar 

  50. Agnarsson, U., Glass, S., and Govan, J. R. W, 1989, Fecal isolation of Pseudomonas aeruginosa from patients with cystic fibrosis, J. Clin. Microbiol. 27:96–98.

    PubMed  CAS  Google Scholar 

  51. Kessner, D. M., and Lepper, M. H., 1967, Epidemiologic studies of gram-negative bacilli in the hospital and community, Am. J. Epidemiol. 85:45–60.

    PubMed  CAS  Google Scholar 

  52. Bruce, M. C., Poncz, L., Klinger, J. D., Stern, R. C., Tomashefski, J. E, Jr., and Dearborn, D. G., 1985, Biochemical and pathological evidence for proteolytic destruction of lung connective tissue in cystic fibrosis, Am. Rev. Respir. Dis. 132:529–535.

    PubMed  CAS  Google Scholar 

  53. Buck, A. C., and Cooke, E. M., 1969, The fate of ingested Pseudomonas aeruginosa in normal persons, J. Med. Microbiol. 2:521–525.

    Article  PubMed  CAS  Google Scholar 

  54. Pierce, A. K., and Sanford, J. E, 1974, Aerobic gram-negative bacillary pneumonias, Am. Rev. Respir. Dis. 110:647–658.

    PubMed  CAS  Google Scholar 

  55. Jackson, A. E., Southern, P. M., Pierce, A. K., Fallis, B. D., and Sanford, J. P, 1967, Pulmonary clearance of gram-negative bacilli, J. Lab. Clin. Med. 69:833–841.

    PubMed  CAS  Google Scholar 

  56. Salata, R. A., Lederman, M. M., Shlaes, D. M., Jacobs, M. R., Eckstein, E., Tweardy, D., Toossy, Z., Chielewski, R., Marino, J., King, C. H. Graham, R. C., and Ellner, J. J., 1987, Diagnosis of nosocomial pneumonia in intubated intensive care unit patients, Am. Rev. Respir. Dis. 135:426–432.

    PubMed  CAS  Google Scholar 

  57. Woods, D. E., Straus, D. C., Johanson, W. G., Jr., and Bass, J. A., 1981, The role of fibronectin in the prevention of adherence of Pseudomonas aeruginosa to buccal cells, J.Infect. Dis. 143: 784–790.

    Article  PubMed  CAS  Google Scholar 

  58. Suter, S., Schaad, U. B., Morgenthaler, J. J., Chevallier, I., and Schnebli, H. E., 1988, Fibronectin-cleaving activity in bronchial secretions of patients with cystic fibrosis,J. Infect. Dis. 158:89–100.

    Article  PubMed  CAS  Google Scholar 

  59. Smallman, L. A., Hill, S. L., and Stockley, R. A., 1984, Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: A serine proteinase effect, Thorax 39: 663–667.

    Article  PubMed  CAS  Google Scholar 

  60. Niederman, M. S., Merrill, W. W, Polomski, L. M., Reynolds, H. Y., and Gee, J. B. L., 1986, Influence of sputum IgA and elastase on tracheal cell bacterial adherence, Am. Rev. Respir. Dis. 133:255–260.

    PubMed  CAS  Google Scholar 

  61. Döring, G., Goldstein, W, Botzenhart, K., Kharazmi, A., Schiøtz, P. O., Høby, N., and Dasgupta, M., 1986, Elastase from polymorphonuclear leucocytes: A regulatory enzyme in immune complex disease, Clin. Exp. Immunol. 64:597–605.

    PubMed  Google Scholar 

  62. Ramphal, R., Small, P. A., Shands, J. W. Jr., Fischweiger, W., and Small, P. A., Jr., 1980, Adherence of Pseudomonas aeruginosa to tracheal cells injured by influenza infection or by endotracheal intubation, Infect. Immun. 27:614–619.

    PubMed  CAS  Google Scholar 

  63. Ramphal, R., and Pyle, M., 1983, Adherence of mucoid and nonmucoid Pseudomonas aeruginosa to acid-injured tracheal epithelium, Infect. Immun. 41:345–351.

    PubMed  CAS  Google Scholar 

  64. Plotkowski, M. C., Beck, G., Tournier, J.M., Bernardo-Filho, M., Marques, E. A., and Puchelle, E., 1989, Adherence of Pseudomonas aeruginosa to respiratory epithelium and the effect of leucocyte elastase, J. Med. Microbiol. 30:285–293.

    Article  PubMed  CAS  Google Scholar 

  65. Döring, G., and Dauner, H.-J., 1988, Clearance of Pseudomonas aeruginosa in different rat lung models, Am. Rev. Respir. Dis. 138:1249–1253.

    PubMed  Google Scholar 

  66. Dal Nogare, A. R., Toews, G. B., and Pierce, A. K., 1987, Increased salivary elastase precedes gram-negative bacillary colonization in postoperative patients, Am. Rev. Respir. Dis. 135:671–675.

    Google Scholar 

  67. Bedrossian, C. W. M., Greenberg, S. D., Singer, D. B., Hansen, J. J., and Rosenberg, H. S., 1976, The lung in cystic fibrosis: A quantitative study including prevalence of pathologic findings among different age groups, Hum. Pathol. 7:195–204.

    Article  PubMed  CAS  Google Scholar 

  68. Martin, T. R., Rubens, C. E., and Wilson, C. B., 1988, Lung antibacterial defense mechanisms in infant and adult rats: Implications for the pathogenesis of group B streptococcal infections in the neonatal lung, J. Infect. Dis. 157:91–100.

    Article  PubMed  CAS  Google Scholar 

  69. Hemming, V. G., Overall, J. C., and Britt, M. R., 1976, Nosocomial infections in a newborn intensive care unit. Results of forty-one months of surveillance, N. Eng. J. Med. 294:1310-1316.

    Article  CAS  Google Scholar 

  70. Berger, M., 1990, Complement deficiency and neutrophil dysfunction as risk factors for bacterial infection in newborns and the role of granulocyte transfusion in therapy, Rev. Infect. Dis. 12:S401–S409.

    Article  PubMed  Google Scholar 

  71. Baltimore, R. S., Christie, C. D. C., and Smith, G. J. W., 1989, Immunohistopathologic location of Pseudomonas aeruginosa in lungs of patients with cystic fibrosis, Am. Rev. Respir. Dis. 140:1650–1661.

    Article  PubMed  CAS  Google Scholar 

  72. Cash, H. A., Woods, D. E., McCullough, B., Johanson, W. G., Jr., and Bass, J. A., 1979, A rat model of chronic respiratory infection with Pseudomonas aeruginosa,Am. Rev. Respir. Dis. 119:453–459.

    PubMed  CAS  Google Scholar 

  73. Römling, U., Grothus, D., and Tümmler, B., 1991, Whole DNA genome typing, Antibiot. Chemother. 44:1–7.

    PubMed  Google Scholar 

  74. Woods, D. E., Straus, D. C., Johanson, W. G., Jr., Berry, V. K., and Bass, J. A., 1980, Role of pili in adherence of Pseudomonas aeruginosa to mammalian buccal epithelial cells, Infect. Immun. 29:1146–1151.

    PubMed  CAS  Google Scholar 

  75. Ramphal, R., Sadoff, J. C., Pyle, M., and Silipigni, J. D., 1984, Role of pili in adherence of Pseudomonas aeruginosa to injured tracheal epithelium, Infect. Immun. 44:38–40.

    PubMed  CAS  Google Scholar 

  76. Doig, P., Todd, T., Sastry, P. A., Lee, K. K., Hodges, R. S., Paranchych, W, and Irvin, R. T., 1988, Role of pili in adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells, Infect. Immun. 56:1641–1646.

    PubMed  CAS  Google Scholar 

  77. Lee, K. K., Doig, E., Irvin, R. T., Paranchych, W., and Hodges, R. S., 1989, Mapping the surface regions of Pseudomonas aeruginosa PAK pilin: The importance of the C-terminal region for adherence to human buccal epithelial cells, Mol. Microbiol. 30:285–293.

    Google Scholar 

  78. Baker, N., and Marcus, H., 1980, Adherence of clinical isolates of Pseudomonas aeruginosa to hamster tracheal epithelium in vitro, Curr. Microbiol. 7:35–40.

    Article  Google Scholar 

  79. Vishwanath, S., and Ramphal, R., 1985, Tracheobronchial mucin receptors for Pseudomonas aeruginosa. Predominance of amino sugars in binding sites, Infect. Immun. 48:331–335.

    PubMed  CAS  Google Scholar 

  80. Ramphal, R., and Pyle, M., 1983, Evidence for mutins and sialic acid as receptors for Pseudomonas aeruginosa in the lower respiratory tract, Infect. Immun. 41:339–344.

    PubMed  CAS  Google Scholar 

  81. Baker, N., and Svanborg-Eden, C., 1989, Role of alginate in the adherence of Pseudomonas aeruginosa, Antibiot. Chemother. 42:72–79.

    PubMed  CAS  Google Scholar 

  82. Ramphal, R., Carnoy, C., Fievre, S., Michalski, J.-C., Houdret, N., Lamblin, G., Strecker, G., and Roussel, E., 1991, Pseudomonas aeruginosa recognizes carbohydrate chains containing type 1 (Gal(31–3GIcNac) or type 2 (Galβl-4G1cNac) disaccharide units, Infect. Immun. 59: 700–704.

    PubMed  CAS  Google Scholar 

  83. Doggett, R. G., Harrison, G. M., Stilwell, R. N., and Wallis, E. S., 1966, An atypical Pseudomonas aeruginosa associated with cystic fibrosis of the pancreas, J. Pediatr. 68:628–635.

    Google Scholar 

  84. Doggett, R. G., and Harrison, G. M., 1972, Pseudomonas aeruginosa: Immune status in patients with cystic fibrosis, Infect. Immun. 6:628–635.

    PubMed  CAS  Google Scholar 

  85. Lam, J., Chan, R., Lam, K., and Costerton, J. W, 1980, Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis, Infect. Immun. 28: 546–556.

    PubMed  CAS  Google Scholar 

  86. Linker, A., and Jones, R. A., 1964, A new polysaccharide resembling alginic acid from a Pseudomonas microorganism, Nature 204:187–188.

    Article  PubMed  CAS  Google Scholar 

  87. Pier, G. B., Desjardins, D., Aguilar, T., Barnard, M., and Speert, D. P, 1986, Polysaccharide surface antigens expressed by nonmucoid isolates of Pseudomonas aeruginosa from cystic fibrosis patients, J. Clin. Microbiol. 24:189–196.

    PubMed  CAS  Google Scholar 

  88. Doig, E, Smith, N. R., Todd, T., and Randall, T J., 1987, Characterization of the binding of Pseudomonas aeruginosa alginate to human epithelial cells, Infect. Immun. 55:1517–1522.

    PubMed  CAS  Google Scholar 

  89. Baker, N., Minor, V., Deal, C., Sharabadi, M. S., Simpson, D. A., and Woods, D. E., 1991, Pseudomonas aeruginosa exoenzyme-S is an adhesin, Infect. Immun., 59:2859–2863.

    PubMed  CAS  Google Scholar 

  90. Ramphal, R., Koo, L., Ishimoto, K. S., Totten, P. A., Lara, J. C., and Lory, S., 1991, Adhesion of Pseudomonas aeruginosa pilin-deficient mutants to mutin, Infect. Immun. 59:1307–1311.

    PubMed  CAS  Google Scholar 

  91. Simel, D. L., Masten, B. S., Pratt, P. C., Wisseman, C. L., Shelburne, J. D., and Spock, A., 1984, Scanning electron microscopic study of the airways in normal children and in patients with cystic fibrosis and other lung diseases, Pediatr. Pathol. 2:47–64.

    Article  PubMed  CAS  Google Scholar 

  92. Jeffery, P. K., and Brain, A. P. R., 1988, Surface morphology of human airway mucosa: Normal, carcinoma, or cystic fibrosis, Scanning Electron Microsc. 2:553–560.

    CAS  Google Scholar 

  93. Chi, E., Mehl, T, Nunn, D., and Lory, S., 1991, Interaction of Pseudomonas aeruginosa with A549 pneumocyte cells, Infect. Immun. 59:822–828.

    PubMed  CAS  Google Scholar 

  94. Liu, P. V., 1974, Extracellular toxins of Pseudomonas aeruginosa, J. Infect. Dis. 130:S94–S99.

    Article  PubMed  Google Scholar 

  95. Meyers, D. J., and Berk, R. S., 1990, Characterization of phospholipase C from Pseudomonas aeruginosa as a potent inflammatory agent, Infect. Immun. 58:659–666.

    PubMed  CAS  Google Scholar 

  96. Husson, M. O., Mielcarek, C., Gavini, E, Caron, C., Izard, D., and Leclerc, H., 1989, Isolation and characterization of monoclonal antibodies against alkaline phosphatase of Pseudomonas aeruginosa, J. Clin. Microbiol. 27:1115–1118.

    PubMed  CAS  Google Scholar 

  97. Wretlind, B., and Pavlovskis, O. E, 1983, Pseudomonas aeruginosa elastase and its role in Pseudomonas infections, Rev. Infect. Dis. 5:S998–S1004.

    Article  PubMed  CAS  Google Scholar 

  98. Nicas, T. I., and Iglewski, B. H., 1985, The contribution of exoproducts to virulence of Pseudomonas aeruginosa, Can. J. Microbiol. 31:387–392.

    Article  PubMed  CAS  Google Scholar 

  99. Döring, G., Maier, M., Müller, E., Bibi, Z., Tümmler, B., and Kharazmi, A., 1987, Virulence factors of Pseudomonas aeruginosa, Antibiot. Chemother. 39:136–148.

    PubMed  Google Scholar 

  100. Leisinger, T., and Margraff, R., 1979, Secondary metabolites of the fluorescent Pseudo-monads, Microbiol. Rev. 43:422–442.

    PubMed  CAS  Google Scholar 

  101. Woods, D. E., Th, M., and Sokol, P. A., 1989, Pseudomonas aeruginosa exoenzyme S as a pathogenic determinant in respiratory infection, Antibiot. Chemother. 44:27–35.

    Google Scholar 

  102. Pedersen, S. S., Hβiby, N., Espersen E, and Kharazmi, A., 1991, Alginate in infection, Antibiot. Chemother: 44:68–79.

    PubMed  CAS  Google Scholar 

  103. Hayashi, T., and Terawaki, Y., 1991, Molecular approach to Pseudomonas aeruginosa cytotoxin: Structure, activation mechanism and phage conversion, Antibiot. Chemother. 44: 48–53.

    PubMed  CAS  Google Scholar 

  104. Lutz, E, Xiong, G., Jungblut, R., Orlik-Eisel, G., Göbel-Reifert, A., and Leidolf, R., 1991, Pore-forming cytotoxin of Pseudomonas aeruginosa: Molecular effects and aspects of pathogenicity, Antibiot. Chemother: 44:54–58.

    PubMed  CAS  Google Scholar 

  105. Vasil, M. L., Graham, I.. M., Ostroff, R. M., Shortridge, V. D., and Vasil, A. I., 1991, Phospholipase C: Molecular biology and contribution to the pathogenesis of Pseudomonas aeruginosa,Antibiot. Chemother 44:34–47.

    PubMed  CAS  Google Scholar 

  106. Jaeger, K.-E., Kharazmi, A., and Høby, N., 1991, Extracellular lipase of Pseudomonas aeruginosa: Biochemical characterization and effect on human neutrophil and monocyte function in vitro, Microb. Pathogen., in press.

    Google Scholar 

  107. Wolz, C., Hellstem, E., Haug, M., Galloway, D. R., Vasil, M. K., and Döring, G., 1991, Pseudomonas aeruginosa LasB mutant constructed by insertional mutagenesis reveals elastolytic activity due to alkaline proteinase of LasA fragment, Mol. Microbiol. 5:2125–2131.

    Article  PubMed  CAS  Google Scholar 

  108. Steuhl, K. P., Döring, G., Henni, A., Thiel, H. J., and Botzenhart, K., 1987, Relevance of host-derived and bacterial factors in Pseudomonas aeruginosa corneal infections, Invest. Ophthalmol. Vis. Sci. 28:1559–1568.

    PubMed  CAS  Google Scholar 

  109. Döring, G., Obernesser, H. J., and Botzenhart, K., 1981, Extracellular toxins of Pseudomonas aeruginosa. II. Effect of two proteases on human immunoglobulins IgG, IgA and secretory IgA, Zentralbl. Bakteriol. Mikrobiol. Hyg. (A) 249:89–98.

    Google Scholar 

  110. Schultz, D. R., and Miller, K. D., 1974, Elastase of Pseudomonas aeruginosa: Inactivation of complement components and complement-derived chemotactic and phagocytic factors, Infect. Immun. 10:128–135.

    PubMed  CAS  Google Scholar 

  111. Döring, G., Pfestorf, M., Botzenhart, K., and Abdallah, M. A., 1988, Impact of proteases on iron uptake of Pseudomonas aeruginosa pyoverdin from transferrin and lactoferrin, Infect. Immun. 56:291–293.

    PubMed  Google Scholar 

  112. Kharazmi, A., 1989, Interactions of Pseudomonas aeruginosa proteases with the cells of the immune system, Antibiot. Chemother. 42:42–49.

    PubMed  CAS  Google Scholar 

  113. Ankenbauer, R., Sriyosachati, S., and Cox, C. D., 1985, Effects of siderophores on the growth of Pseudomonas aeruginosa in human serum and transferrin, Infect. Immun. 49: 132–140.

    PubMed  CAS  Google Scholar 

  114. Sorensen, R. U., Fredricks, D. N., and Waller, R. L., 1991, Inhibition of normal and malignant cell proliferation by pyocyanine and 1-hydroxyphenazine, Antibiot. Chemother. 44: 85–93.

    PubMed  CAS  Google Scholar 

  115. Pitt, T. L., 1989, Lipopolysaccharide and virulence of Pseudomonas aeruginosa, Antibiot. Chemother. 42:1–7.

    PubMed  CAS  Google Scholar 

  116. Wick, M. J., Frank, D. W., Storey, D. G., and Iglewski, B. H., 1990, Structure, function and regulation of Pseudomonas aeruginosa exotoxin A, Ann. Rev. Microbiol. 44:335–363.

    Article  CAS  Google Scholar 

  117. Galloway, D. R., Pseudomonas aeruginosa elastase and elastolysis, 1991, Mol. Microbiol. 5:2315–2321.

    Article  PubMed  CAS  Google Scholar 

  118. Sabath, D. E. (ed.), 1980, Pseudomonas aeruginosa, the Organism, Diseases it Causes and their Treatment, Hans Huber Publ., Bern.

    Google Scholar 

  119. Moss, R. B., and Lewiston, N. J., 1984, Immunopathology of cystic fibrosis, in: Immunological Aspects of Cystic Fibrosis (E. Shapira and G. B. Wilson, eds.), CRC Press, Boca Raton, Florida, pp. 5–28.

    Google Scholar 

  120. Döring, G., Albus, A., and Hβiby, N., 1988, Immunological aspects of cystic fibrosis, Chest 94:S109–S114.

    Google Scholar 

  121. Middlebrook, J. L., and Dorland, R. B., 1984, Bacterial toxins: Cellular mechanisms of action, Microbiol. Rev. 48:199–221.

    PubMed  CAS  Google Scholar 

  122. FitzGerald, D., Morris, R., and Saelinger, C., 1980, Receptor-mediated entry of Pseudomonas toxin by mouse fibroblasts, Cell 21:867–873.

    Article  PubMed  CAS  Google Scholar 

  123. Iglewski, B. H., and Kabat, D., 1975, NAD-dependent inhibitions of protein synthesis by Pseudomonas aeruginosa toxin, Proc. Natl. Acad. Sci. USA 72:2284–2288.

    Article  PubMed  CAS  Google Scholar 

  124. Collier, R. J., 1975, Diphtheria toxin: Mode of action and structure, Bacteriol. Rev. 39: 54–85.

    PubMed  CAS  Google Scholar 

  125. Goldstein, E., and Hoeprich, P D., 1977, Diphtheria, in: Infectious diseases (P. D. Hoeprich, ed.), Harper and Row, San Francisco, pp. 247–258.

    Google Scholar 

  126. Klinger, J. D., Straus, D.C., Hilton, C. B., and Bass, J. A., 1978, Antibodies to proteases and exotoxin A of Pseudomonas aeruginosa in patients with cystic fibrosis: Demonstration by radioimmunoassay, J. Infect. Dis. 138:49–58.

    Article  PubMed  CAS  Google Scholar 

  127. Döring, G., Goldstein, W, Röll, W, Schiøtz, R O., Høby, N., and Botzenhart, K., 1985, Role of Pseudomonas aeruginosa exoenzymes in lung infections of patients with cystic fibrosis, Infect. Immun. 49:557–562.

    PubMed  Google Scholar 

  128. Gray, G. L., Smith, D. H., Baldridge, J. S., Hoskins, R. N., Vasil, M. L., Chen, E. Y., and Heyneker, H. L., 1984, Cloning, nucleotide sequence, and expression in Escherichia coli of the exotoxin A structural gene of Pseudomonas aeruginosa, Proc. Natl. Acad. Sci. USA 81: 2645–2649.

    Article  PubMed  CAS  Google Scholar 

  129. Greenfield, L., Bjorn, M. J., Horn, G., Fong, D., Buck, G. A., Collier, R. J., and Kaplan, D. A., 1983, Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage β, Proc. Natl. Acad. Sci. USA 80:6853–6857.

    Article  PubMed  CAS  Google Scholar 

  130. Goldstein, W., and Döring, G., 1986, Lysosomal enzymes from polymorphonuclear leukocytes and proteinase inhibitors in patients with cystic fibrosis, Am. Rev. Respir. Dis. 134: 49–56.

    PubMed  CAS  Google Scholar 

  131. Döring, G., and Müller, E., 1989, Different sensitivity of Pseudomonas aeruginosa exotoxin A and diphtheria toxin to enzymes from polymorphonuclear leukocytes, Microb. Pathogen. 6: 287–295.

    Article  Google Scholar 

  132. Döring, G., Obernesser, H. J., Botzenhart, K., Flehmig, B., Høiby, N., and Hofmann, A., 1983, Proteases of Pseudomonas aeruginosa in patients with cystic fibrosis, J. Infect. Dis. 147: 744–750.

    Article  PubMed  Google Scholar 

  133. Döring, G., and Høiby, N., 1983, Longitudinal study of immune response to Pseudomonas aeruginosa antigens in cystic fibrosis, Infect. Immun. 42:197–201.

    PubMed  Google Scholar 

  134. Jagger, K. S., Robinson, D. L., Franz, M. N., and Warren, R. L., 1982, Detection by enzyme-linked immunosorbent assays of antibody specific for Pseudomonas proteases and exotoxin A in sera from cystic fibrosis patients, J. Clin. Microbiol. 15:1054–1058.

    PubMed  CAS  Google Scholar 

  135. Granström, M., Ericsson, A., Strandvik, B., Wretlind, B., Pavlovskis, O. R., Berka, R., and Vasil, M. L., 1984, Relation between antibody response to Pseudomonas aeruginosa exoproteins and colonization/infection in patients with cystic fibrosis, Acta Paediatr. Scand. 73: 772–777.

    Article  PubMed  Google Scholar 

  136. Hancock, R. E. W., Movat, E. C. A., and Speert, D. P., 1984, Quantitation and identification of antibodies to outer membrane proteins of Pseudomonas aeruginosa in sera of patients with cystic fibrosis, J. Infect. Dis. 149:220–226.

    Article  PubMed  CAS  Google Scholar 

  137. Shand, G. H., Pedersen, S. S., Lam, K., and Høby, N., 1989, Iron-regulated outer membrane proteins and virulence in Pseudomonas aeruginosa, Antibiot. Chemother. 42:15–26.

    PubMed  CAS  Google Scholar 

  138. Brett, M. M., Ghoneim, A. T. M., and Littlewood, J. M., 1987, Serum IgG antibodies in patients with cystic fibrosis with early Pseudomonas aeruginosa infection, Arch. Dis. Child. 62: 357–361.

    Article  PubMed  CAS  Google Scholar 

  139. Moss, R. B., Hsu, Y.-P., Lewiston, N. J Curd, J. G., Milgrom, H., Hart, S., Dyer, B. and Larrick, J. W., 1986, Association of specific immune complexes, complement activation and antibodies to Pseudomonas aeruginosa lipopolysaccharide and exotoxin A with mortality in cystic fibrosis, Am. Rev. Respir. Dis. 133:648–652.

    PubMed  CAS  Google Scholar 

  140. Pedersen, S. S., Espersen, R., and Høiby, N., 1987, Diagnosis of chronic Pseudomonas aeruginosa infection in cystic fibrosis by enzyme-linked immunosorbent assay, J. Clin. Microbiol. 25:1830–1836.

    PubMed  CAS  Google Scholar 

  141. Bryan, L. E., Kureishi, A., and Rabin, H. R.., 1983, Detection of antibodies to Pseudomonas aeruginosa alginate extracellular polysaccharide in animals and cystic fibrosis patients by enzyme-linked immunosorbent assay, J. Clin. Microbiol. 18:276–282.

    PubMed  CAS  Google Scholar 

  142. Albus, A., Saalmann, M., Tesch, W., Pedersen, S. S., and Döring, G., 1989, Increased levels of IgG subclasses, specific for Pseudomonas aeruginosa protein and polysaccharide antigens in chronically infected patients with cystic fibrosis, Acta Pathol. Microbiol. Immunol. Scand. 97:1146–1148.

    CAS  Google Scholar 

  143. Pedersen, S. S., Høby, N., Shand, G. H., and Pressler, T., 1989, Antibody response to Pseudomonas aeruginosa antigens in cystic fibrosis, Antibiot. Chemother. 42:130–153.

    PubMed  CAS  Google Scholar 

  144. Döring, G., Buhl, V., Høiby, N., Schiøtz, P.O., and Botzenhart, K., 1984, Detection of proteases of Pseudomonas aeruginosa in immune complexes isolated from sputum of cystic fibrosis patients, Acta Pathol. Microbiol. Immunol. Scand. (C) 92:307–312.

    Google Scholar 

  145. Kownatzki, R., Tümmler, B., and Döring, G., 1987, Rhamnolipid of Pseudomonas aeruginosa in sputum of cystic fibrosis patients, Lancet i:1026–1027.

    Article  Google Scholar 

  146. Finlay, B. B., and Falkow, S., 1989, Common themes in microbial pathogenicity, Microbiol. Rev. 53:210–230.

    PubMed  CAS  Google Scholar 

  147. Clerc, P. L., Ryter, A., Mounier, J., and Sansonetti, P J., 1987, Plasmid-mediated early killing of eucaryotic cells by Shigella flexneri as studied by infection of J774 macrophages, Infect. Immun. 55:521–527.

    PubMed  CAS  Google Scholar 

  148. Sansonetti, P. J., and Mounier, J., 1987, Metabolic events mediating early killing of host cells infected by Shigella flexneri, Microb. Pathogen. 3:53–61.

    Article  CAS  Google Scholar 

  149. Colt, H. G., Holden, W. E., and Kaplan, S. S., 1990, On septicemia in an adult with cystic fibrosis: Neutrophil function and serum chemoattractant activity, Pediatr. Pulmonol. 6:63–64.

    Article  Google Scholar 

  150. Miller, J. F., Mekalanos, J. J., and Falkow, S., 1989, Coordinate regulation and sensory transduction in the control of bacterial virulence, Science 243:916–922.

    Article  PubMed  CAS  Google Scholar 

  151. Higgins, C. E, Hinton, J. C. D., Hulton, C. S. J., Owen-Hughes, T., Pavitt, G. D., and Seirafi, A., 1990, Protein H1: A role for chromatin structure in the regulation of bacterial gene expression and virulence? Mol. Microbiol. 4:2007–2012.

    Article  PubMed  CAS  Google Scholar 

  152. Knowles, M. R., Stutts, M. J., Spock, A., Fischer, N., Gutzy, J. J., and Boucher, R. C., 1983, Abnormal ion permeation through cystic fibrosis respiratory epithelium, Science 221:1067–1070.

    Article  PubMed  CAS  Google Scholar 

  153. Dalhoff, A., and Döring, G., 1987, Action of quinolones on gene expression and bacterial membranes, Antibiot. Chemother. 39:205–214.

    PubMed  CAS  Google Scholar 

  154. Terry, J. M., Pina, S. E., and Mattingly, S. J., 1991, Environmental conditions which influence mucoid conversion in Pseudomonas aeruginosa PAOI, Infect. Immun. 59:471–477.

    PubMed  CAS  Google Scholar 

  155. Deretic, V., Govan, J. R. W, Konyecsni, W. M., and Martin, D. W, 1990, Mucoid Pseudomonas aeruginosa in cystic fibrosis: Mutations in the muc loci affect transcription of the algR and algD genes in response to environmental stimuli, Mol. Microbiol. 4:189–198.

    Article  PubMed  CAS  Google Scholar 

  156. Roychoudhury, S., Zielinski, N. A., DeVault, J. D., Kato, J., Shinabarger, D. L., May, T. B., Maharaj, R., Kimbara, K., Misra, T. K., and Chakrabarty, A. M., 1991, Pseudomonas aeruginosa infection in cystic fibrosis: Biosynthesis of alginate as a virulence factor, Antibiot. Chemother . 44:63–67.

    PubMed  CAS  Google Scholar 

  157. Schultz, E. W., 1947, A gelatinous variant of Pseudomonas aeruginosa, Proc. Soc. Exp. Biol. Med. 65:289–291.

    PubMed  CAS  Google Scholar 

  158. McAvoy, M. J., Newton, V., Paull, A., Morgan, J., Gacesa, E., and Russell, N.J., 1989, Isolation of mucoid strains of Pseudomonas aeruginosa from non-cystic-fibrosis patients and characterization of the structure of their secreted alginate, J. Med. Microbiol. 28:183–189.

    Article  PubMed  CAS  Google Scholar 

  159. Stevens, D., Lieberman, M., McNitt, T., and Price, J 1984, Demonstration of uronic acid capsular material in the cerebrospinal fluid of a patient with meningitis caused by mucoid Pseudomonas aeruginosa, J. Clin. Microbiol. 19:942–943.

    PubMed  CAS  Google Scholar 

  160. Anastassiou, E. D., Frangidis, C., and Dimitracopoulos, G., 1986, Nonfatal bacteremia caused by a mucoid, alginate-producing strain of Pseudomonas aeruginosa, Diagn. Microbiol. Infect. Dis. 5:277–283.

    Article  PubMed  CAS  Google Scholar 

  161. McCarthy, V. P., Rosenberg, G., Rosenstein, B. J., and Hubbard, V. S., 1986, Mucoid Pseudomonas aeruginosa from a patient without cystic fibrosis: Implications and review of the literature, Pediatr. Infect. Dis. 5:256–258.

    Article  PubMed  CAS  Google Scholar 

  162. Homma, H., Yamanakam, A., Tanimoto, H., Tamura, M., Chijimatsu, Y., Kira, S., and Izumi, T., 1983, Diffuse panbronchiolitis, a disease of the transitional zone of the lung, Chest 83:63–69.

    Article  PubMed  CAS  Google Scholar 

  163. Woods, D. E., Sokol, P. A., Bryan, L. E., Storey, D. G., Mattingly, S. J., Vogel, H. J., and Ceri, H., 1991, In vivo regulation of virulence in Pseudomonas aeruginosa associated with genetic rearrangement,Infect. Dis. 163:143–149.

    Article  CAS  Google Scholar 

  164. Bayer, A. S., Eftekhar, E., Tu, J., Nast, C. C., and Speert, D. P., 1990, Oxygen-dependent up-regulation of mucoid exopolysaccharide (alginate) production in Pseudomonas aeruginosa, Infect. Immun. 58:1344–1349.

    PubMed  CAS  Google Scholar 

  165. Speert, D. P., Farmer, S. W., Campbell, M. E., Musser, J. M., Selander, R. K., and Kuo, S., 1990, Conversion of Pseudomonas aeruginosa to the phenotype characteristic of strains from patients with cystic fibrosis, J. Clin. Microbiol. 28:188–194.

    PubMed  CAS  Google Scholar 

  166. Brown, M. R. W., and Williams, P., 1985, The influence of environment on envelope properties affecting survival of bacteria in infections, Annu. Rev. Microbiol. 39:527–556.

    Article  CAS  Google Scholar 

  167. Hancock, R. E. W., Mutharia, L. M., Chan, L., Darveau, R. P, Speert, D. P, and Pier, G. B., 1983, Pseudomonas aeruginosa isolates from patients with cystic fibrosis: A class of serumsensitive, nontypable strains deficient in lipopolysaccharide O side chains, Infect. Immun. 42:170–177.

    PubMed  CAS  Google Scholar 

  168. Ojeniyi, B., Baek, L., and Høby, N., 1985, Polyagglutinability due to loss of 0-antigenic determinants in Pseudomonas aeruginosa strains isolated from cystic fibrosis patients, Acta Pathol. Microbiol. Scand. [B] 93:7–13.

    CAS  Google Scholar 

  169. Anwar, H., Brown, M. r. W., Day, D. A., and Weller, P. H., 1984, Outer membrane antigens of mucoid Pseudomonas aeruginosa isolated directly from the sputum of a cystic fibrosis patient, FEMS Microbiol. Lett. 24:235–239.

    Article  CAS  Google Scholar 

  170. Shand, G. H., Pedersen, S. S., Lam, K., and Høiby, N., 1989, Iron-regulated outermembrane proteins and virulence in Pseudomonas aeruginosa, Antibiot. Chemother. 42:15–26.

    PubMed  CAS  Google Scholar 

  171. Mohr, C. D., Rust, L., Albus, A. M., Iglewski, B. H., and Deretic, V., 1990, Expression patterns of genes encoding elastase and controlling mucoidy: Co-ordinate regulation of two virulence factors in Pseudomonas aeruginosa isolates from cystic fibrosis, Mol. Microbiol. 4:2103–2110.

    Article  PubMed  CAS  Google Scholar 

  172. Kharazmi, A., Schiøtz, P. O., Høby, N., Baek, L., and Döring, G., 1986, Demonstration of neutrophil chemotactic activity in the sputum of cystic fibrosis patients with Pseudomonas aeruginosa infection, Eur. J. Clin. Invest. 16:143–148.

    Article  PubMed  CAS  Google Scholar 

  173. Schiøtz, P. O., Sorensen, H., and Høby, N., 1979, Activated complement in the sputum from patients with cystic fibrosis, Acta Pathol. Microbiol. Scand.[C] 87:1–5.

    Google Scholar 

  174. Cromwell, O., Morris, H. R., Hodson, M. E., Walport, M. J., Taylor, G. W., Batten, J., and Kay, A. B., 1981, Identification of leukotrienes D and B in sputum of cystic fibrosis patients, Lancet ii:164–165.

    Article  Google Scholar 

  175. Fontan, P. A., Garcia, V. E., Cerquetti, M. C., and Sordelli, D. O., 1989, Pseudomonas aeruginosa chemotactins (PAC): Preliminary characterization, Annu. Meet. Am. Soc. Microbiol., B235.

    Google Scholar 

  176. Cabral, D. A., Loh, B. A., and Speert, D. P, 1987, Mucoid Pseudomonas aeruginosa resists nonopsonic phagocytosis by human neutrophils and macrophages, Pediatr. Res. 22: 429–431.

    Article  PubMed  CAS  Google Scholar 

  177. Young, L. S., and Armstrong, D., 1972, Human immunity to Pseudomonas aeruginosa. In vitro interaction of bacteria, polymorphonuclear leukocytes and serum factors, J. Infect. Dis. 126:257–276.

    Article  PubMed  CAS  Google Scholar 

  178. Leslie, R. G. Y., and Alexander, M. D., 1979, Cytophilic antibodies, Curr. Top. Microbial. Immunol. 88:26–104.

    Google Scholar 

  179. Reynolds, H. Y., 1974, Pulmonary host defenses in rabbits after immunization with Pseudomonas antigens: The interaction of bacteria, antibodies, macrophages and lymphocytes, J. Infect. Dis. 130:S134–S142.

    Article  PubMed  Google Scholar 

  180. Thomassen, M. J., Boxerbaum, B., Demko, C. A., Kuchenbrod, P. J., Dearborn, D. G., and Wood, R. E., 1979, Inhibitory effect of cystic fibrosis serum on Pseudomonas phagocytosis by rabbit and human alveolar macrophages, Pediatr. Res. 13:1085–1088.

    Article  PubMed  CAS  Google Scholar 

  181. Shryock, T. R., Mollé, J. S., Klinger, J. D., and Thomassen, M. J., 1986, Association with phagocytic inhibition of anti-Pseudomonas aeruginosa immunoglobulin G antibody subclass levels in serum from patients with cystic fibrosis, J. Clin. Microbiol. 23:513–516.

    PubMed  CAS  Google Scholar 

  182. Fick, R. B., Olchowski, J., Squier, S. U., Merrill, W W, and Reynolds, H. Y., 1986, Immunoglobulin G subclasses in cystic fibrosis. IgG2 response to Pseudomonas aeruginosa lipopolysaccharide, Am. Rev. Respir. Dis. 133:418–422.

    PubMed  Google Scholar 

  183. Moss, R. B., Hsu, Y.-P, Sullivan, M. M., and Lewiston, N. J., 1986, Altered antibody isotype in cystic fibrosis: Possible role in opsonic deficiency, Pediatr. Res. 20:453–459.

    Article  PubMed  CAS  Google Scholar 

  184. Moss, R. B., Hsu, Y.-E., van Eede, P. H., Van Leeuwen, M. V, Lewiston, N.J., and De Lange, G., 1987, Altered antibody isotype in cystic fibrosis. Impaired natural antibody response to polysaccharide antigens, Pediatr. Res. 22:708–713.

    Article  PubMed  CAS  Google Scholar 

  185. Pressler, T., Mansa, B., Jensen, T., Pedersen, S. S., Høiby, N., and Koch, C., 1988, Increased IgG2 and IgG3 concentration is associated with advanced Pseudomonas aeruginosa infection and poor pulmonary function in cystic fibrosis, Acta Paediatr. Scand. 77:576–582.

    Article  PubMed  CAS  Google Scholar 

  186. Eichler, I., Joris, L., Hsu, Y.-P., van Wye, J.,Bram,R., and Moss,R., 1989, Nonopsonic antibodies in cystic fibrosis, J. Clin. Invest. 84:1794–1804.

    Article  PubMed  CAS  Google Scholar 

  187. Thomassen, M. J., Demko, C. A., and Doershuk, C. E, 1987, Cystic fibrosis: A review of pulmonary infections and interventions, Pediatr. Pulmonol. 3:334–351.

    Article  PubMed  CAS  Google Scholar 

  188. Schur, P. H., 1987, IgG subclasses. A review, Ann. Allergy 58:89–99.

    PubMed  CAS  Google Scholar 

  189. Høby, N., Döring, G., and Schiøtz, P. O., 1986, The role of immune complexes in the pathogenesis of bacterial infections, Ann. Rev. Microbiol. 40:29–53.

    Article  Google Scholar 

  190. Döring, G., 1989, Polymorphonuclear leukocyte elastase: Its effects on the pathogenesis of Pseudomonas aeruginosa infection in cystic fibrosis, Antibiol. Chemother. 42:169–176.

    Google Scholar 

  191. Høiby, N., and Koch, C., 1990, Pseudomonas aeruginosa infection in cystic fibrosis and its management, Thorax 45:881–884.

    Article  PubMed  Google Scholar 

  192. Høiby, N., and Axelsen, N. H., 1973, Identification and quantitation of precipitins against Pseudomonas aeruginosa in patients with cystic fibrosis by means of crossed immunoelectrophoresis with intermediate gel, Acta Pathol. Microbiol. Scand. [B] 81:298–308.

    Google Scholar 

  193. Berdischewsky, M., Pollack, M., Young, L. S., Chia, D., Osher, A. B., and Barnett, E. V., 1980, Circulating immune complexes in cystic fibrosis, Pediatr. Res. 14:830–833.

    Article  PubMed  CAS  Google Scholar 

  194. Moss, R. B., and Hsiu, Y.-P, 1982, Isolation and characterization of circulating immune complexes in cystic fibrosis, Clin. Exp. Immunol. 47:301–308.

    PubMed  CAS  Google Scholar 

  195. Pitcher-Wilmott, R. W, Levinsky, R. J., and Matthew, D. J., 1982, Circulating soluble immune complexes containing Pseudomonas antigens in cystic fibrosis, Arch. Dis. Child. 57: 577–581.

    Article  PubMed  CAS  Google Scholar 

  196. Manthei, U., Taussig, L. M., Beckerman, R. C., and Strunk, R. C., 1982, Circulating immune complexes in cystic fibrosis, Am. Rev. Respir. Dis. 126:253–257.

    PubMed  CAS  Google Scholar 

  197. Church, J. A., Jordan, S. C., Keens, T. G., and Wang, C.-I., 1981, Circulating immune complexes in patients with cystic fibrosis, Chest 80:405–411.

    Article  PubMed  CAS  Google Scholar 

  198. Wisnieski, J. J., Todd, E. W., Fuller, R. K., Jones, P. K., Dearborn, D. W., Boat, T. E., and Naff, G. B., 1985, Immune complexes and complement abnormalities in patients with cystic fibrosis. Increased mortality associated with circulating immune complexes and decreased function of the alternative complement pathway, Am. Rev. Respir. Dis. 132:770–777.

    PubMed  CAS  Google Scholar 

  199. Wheeler, W. B., Williams, M., Matthews, W. J., Jr., and Colten, H. R., 1984, Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: 1 5-year longitudinal study,J. Pediatr. 104:695–699.

    Article  PubMed  CAS  Google Scholar 

  200. Dasgupta, M. K., Lam, J., Döring, G., Harley, E L., Zuberbuhler, P, Lam, K., Reichert, A., Costerton, J. W, and Dossetor, J. B., 1987, Prognostic implications of circulating immune complexes and Pseudomonas aeruginosa-specific antibodies in cystic fibrosis, J. Clin. Lab. Immunol. 23:25–30.

    PubMed  CAS  Google Scholar 

  201. Disis, M. L., McDonald, T. L., Colombo, J. L., Kobayashi, R. H., Angle, C. R., and Murray, S., 1986, Circulating immune complexes in cystic fibrosis and their correlation to clinical parameters, Pediatr. Res. 20:385–390.

    Article  PubMed  CAS  Google Scholar 

  202. Dasgupta, M. K., Zuberbuhler, E, Abbi, A., Harley, E. L., Brown, N. E., Lam, K., Dossetor, J. B., and Costerton, J. W., 1987, Combined evaluation of circulating immune complexes and antibodies to Pseudomonas aeruginosa as an immune profile in relation to pulmonary function in cystic fibrosis, J. Clin. Immunol. 7:51–58.

    Article  PubMed  CAS  Google Scholar 

  203. Goldstein, I. M., 1976, Polymorphonuclear leukocyte lysosomes and immune tissue injury, Prog. Allergy 20:301–340.

    Google Scholar 

  204. Suter, S., Schaad, U. B., Roux, L., Nydegger, U. E., and Waldvogel, E. A., 1984, Granulocyte neutral proteases and Pseudomonas elastase as possible causes of airway damage in patients with cystic fibrosis, J. Infect. Dis. 149:523–531.

    Article  PubMed  CAS  Google Scholar 

  205. Tournier, J. M., Jacquot, J., Puchelle, E., and Bieth, J. G., 1985, Evidence that Pseudomonas aeruginosa elastase does not inactivate the bronchial inhibitor in the presence of leukocyte elastase, Am. Rev. Respir. Dis. 132:524–528.

    PubMed  CAS  Google Scholar 

  206. Suter, S., Schaad, U. B., Tegner, H., Ohlsson, K., Desgrandschamps, D., and Waldvogel, E. A., 1986, Levels of free granulocyte elastase in bronchial secretions from patients with cystic fibrosis: Effect of antimicrobial treatment against Pseudomonas aeruginosa, J. Infect. Dis. 153:902–909.

    Article  CAS  Google Scholar 

  207. Jackson, A. H., Hill, S. L., Afford, S. C., and Stockley, R. A., 1984, Sputum solphase proteins and elastase activity in patients with cystic fibrosis, Eur. J. Respir. Dis. 65:114–124.

    PubMed  CAS  Google Scholar 

  208. Fick, R. B., Baltimore, R. S., Squier, S. U., and Reynolds, H. Y., 1985, IgG proteolytic activity of Pseudomonas aeruginosa in cystic fibrosis, J. Infect. Dis. 151:589–598.

    Article  PubMed  Google Scholar 

  209. Döring, G., Goldstein, W, Botzenhart, K., Kharazmi, A., Schiotz, P. 0., H¢iby, N., and Dasgupta, M., 1986, Elastase from polymorphonuclear leukocytes: A regulatory enzyme in immune complex disease, Clin. Exp. Immunol. 64:597–605.

    PubMed  Google Scholar 

  210. Henson, P. M., and Johnston, R. B., Jr., 1987, Tissue injury in inflammation, J. Clin. Invest. 79:669–674.

    Article  PubMed  CAS  Google Scholar 

  211. Johnson, U., Ohlsson, K., and Ohlsson, I., 1976, Effects of granulocyte neutral proteases on complement components, Scand. J. Immunol. 5:421–426.

    Article  PubMed  CAS  Google Scholar 

  212. Tosi, M. E, Zakem, H., and Berger, M., 1990, Neutrophil elastase cleaves C3bi on opsonized Pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch, J. Clin. Invest. 86:300–308.

    Article  PubMed  CAS  Google Scholar 

  213. Berger, M., Sorensen, R. U., Tosi, M. E., Dearborn, D. G., and Döring, G., 1989, Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis, J. Clin. Invest. 84:1302–1313.

    Article  PubMed  CAS  Google Scholar 

  214. Berger, M., 1991, Inflammation in the lung in cystic fibrosis. A vicious cycle that does more harm than good? Clin. Rev. Allergy 9:119–142.

    PubMed  CAS  Google Scholar 

  215. Sommerhoff, C. P, Nadel, J. A., Basbaum, C. B., and Caughey, G. H., 1990, Neutrophil elastase and cathepsin G stimulate secretions from cultured bovine airway gland serous cells, J. Clin. Invest. 85:682–689.

    Article  PubMed  CAS  Google Scholar 

  216. Suter, S., Schaad, U. B., Roux-Lombard, P., Girardin, E., Grau, G., and Dayer, J.-M., 1989, Relation between tumor necrosis factor-a and granulocyte elastase-al-proteinase inhibitor complexes in plasma of patients with cystic fibrosis, Am. Rev. Respir. Dis. 140:1640–1644.

    Article  PubMed  CAS  Google Scholar 

  217. Brown, M. A., Morgan, W. J., Finley, P. R., and Scuderi, P., 1991, Circulating levels of tumor necrosis factor and interleukin-1 in cystic fibrosis, Pediatr. Pulmonol. 10:86–91.

    Article  PubMed  CAS  Google Scholar 

  218. Wilmott, R. W, Kassab, J. T., Kilian, P. L., Benjamin, W. R., Douglas, S. D., and Wood, R. E., 1990, Increased levels of interleukin-1 in bronchoalveolar washings from children with bacterial pulmonary infections, Am. Rev. Respir. Dis. 142:365–368.

    PubMed  CAS  Google Scholar 

  219. Fomsgaard, A., Svenson, M., and Bendtzen, K., 1989, Auto-antibodies to tumor necrosis factor a in healthy humans and patients with inflammatory diseases and gram-negative bacterial infections, Scand. J. Immunol. 30:219–223.

    Article  PubMed  CAS  Google Scholar 

  220. Livermore, D. M., 1989, Role of beta-lactamase and impermeability in the resistance of Pseudomonas aeruginosa, Antibiot. Chemother. 42:257–263.

    PubMed  CAS  Google Scholar 

  221. Cullmann, W, 1989, Mode of action and development of resistance to quinolones, Antibiot. Chemother. 42:287–300.

    PubMed  CAS  Google Scholar 

  222. Gold, R., Carpenter, S., Heuster, H., Corey, M., and Levison, H., 1987, Randomized trial of ceftazidime versus placebo in the management of acute respiratory exacerbations in patients with cystic fibrosis, J. Pediatr. 111:907–913.

    Article  PubMed  CAS  Google Scholar 

  223. Kerem, E., Corey, M., Gold, R., and Levison, H., 1990, Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonization with Pseudomonas aeruginosa, J. Pediatr. 116:714–719.

    Article  PubMed  CAS  Google Scholar 

  224. Regelmann, W. E., Elliott, G. R., Warwick, W. J., and Clawson, C. C., 1990, Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone, Am. Rev. Respir. Dis. 141:914–921.

    PubMed  CAS  Google Scholar 

  225. Michel, B. C., 1988, Antibacterial therapy in cystic fibrosis: A review of the literature published between 1975 and February 1987, Chest 94:S129–S140.

    Google Scholar 

  226. Auerbach, H. S., Williams, M., Kirkpatrick, J. A., and Colton, H. R., 1985, Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis, Lancet 2:686–688.

    Article  PubMed  CAS  Google Scholar 

  227. Rosenstein, B. J., and Eigen, H., 1991, Risks of alternate-day prednisone in patients with cystic fibrosis, Pediatrics 87:245–246.

    PubMed  CAS  Google Scholar 

  228. Donati, M. A., Haver, K., Gerson, W., Klein, M., McLaughlin, E J., and Wohl, M. E. B., 1990, Long-term alternate day prednisone therapy in cystic fibrosis, Pediatr. Pulmonol. (Suppl. 5) 9:A322.

    Google Scholar 

  229. Sordelli, D. O., Cerquetti, M. C., Fontan, P. A., and Meiss, R. P., 1989, Piroxicam treatment protects mice from lethal pulmonary challenge with Pseudomonas aeruginosa, J. Infect. Dis. 159:232–238.

    Article  PubMed  CAS  Google Scholar 

  230. Konstan, M. W, Norvell, T. M., Hilliard, K. A., Shiratsuchi, H., and Berger, M., 1990, Serial bronchoalveolar lavage to evaluate inflammation in cystic fibrosis lung disease, Pediatr. Pulmonol. (Suppl. 5) 9:A309.

    Google Scholar 

  231. Sordelli, D. O., Macri, C. N., and Maille, A. J., 1990, A study of the effect of piroxicam treatment to prevent lung damage in CF patients with Pseudomonas aeruginosa pneumonia, Pediatr. Pulmonol. (Suppl. 5) 9:A217.

    Google Scholar 

  232. Powers, J. C., and Bengali, Z. H., 1986, Elastase inhibitors for treatment of emphysema. Approaches to synthesis and biological evaluation, Am. Rev. Respir. Dis. 134:1097–1100.

    PubMed  CAS  Google Scholar 

  233. Crystal, R. G., 1990, α1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy, J. Clin. Invest. 85:1343–1352.

    Article  PubMed  CAS  Google Scholar 

  234. Sommerhoff, C., Krell, R. D., Williams, J. L., Gomes, B. C., Strimpler, A. M., and Nadel, J. A., 1991, Inhibition of human neutrophil elastase by ICI 200,355, Eur. J. Pharmakol. 193:153–158.

    Article  CAS  Google Scholar 

  235. Rao, N. V., Kennedy, T. E, Rao, G., Ky, N., and Hoidal, J. R., 1990, Sulfated polysaccharides prevent human leukocyte elastase-induced acute lung injury and emphysema in hamsters, Am. Rev. Respir. Dis. 142:407–412.

    PubMed  CAS  Google Scholar 

  236. Smith, R. M., Traber, L. D., Traber, D. L., and Spragg, R. G., 1989, Pulmonary deposition and clearance of aerosolized alpha-1-proteinase inhibitor administered to dogs and to sheep, J. Clin. Invest. 84:1145–1154.

    Article  PubMed  CAS  Google Scholar 

  237. Hubbard, R. C., Casolaro, M. A., Mitchell, M., Sellers, S. E., Arabia, E, Matthay, M. A., and Crystal, R. G., 1989, Fate of aerosolized recombinant DNA-produced a1-antitrypsin: Use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance, Proc. Natl. Acad. Sci. USA 86:680–684.

    Article  PubMed  CAS  Google Scholar 

  238. McElvaney, N. G., Hubbard, R. C., Birrer, P., Chernick, M. S., Caplan, D. B., Frank, M. M., and Crystal, R. G., 1991, Aerosol a-1-antitrypsin treatment for cystic fibrosis, Lancet 337: 392–394.

    Article  PubMed  CAS  Google Scholar 

  239. Pennington, J. E., Reynolds, H. Y., Wood, R. E., Robinson, R. A., and Levine, A. S., 1975, Use of a Pseudomonas aeruginosa vaccine in patients with acute leukemia and cystic fibrosis, Am. J. Med. 58:629–636.

    Article  PubMed  CAS  Google Scholar 

  240. Langford, D. T., and Hiller, J., 1984, Prospective, controlled study of a polyvalent Pseudomonas vaccine in cystic fibrosis—Three year results, Arch. Dis. Child. 59:1131–1133.

    Article  PubMed  CAS  Google Scholar 

  241. Rotering, H., and Dorner, E, 1989, Studies on a Pseudomonas aeruginosa flagella vaccine, Antibiot. Chemother. 42:218–228.

    PubMed  CAS  Google Scholar 

  242. Crowe, B. A., Enzensberger, O., Schober-Bendixen, S., Mitterer, A., Mundt, W., Livey, I., Pabst, H., Kaeser, R., Eibl, M., Eibl, J., and Dorner, E., 1991, The first clinical trial of Immuno’s experimental Pseudomonas aeruginosa flagellar vaccines, Antibiot. Chemother. 44: 143–156.

    PubMed  CAS  Google Scholar 

  243. Finke, M., Muth, G., Reichhelm, T., Thoma, M., Duchene, M., Hungerer, K. D., Domdey, H., and Specht, B.-U., 1991, Protection of immunosuppressed mice against infection with Pseudomonas aeruginosa by recombinant P. aeruginosa lipoprotein I and lipoprotein I-specific monoclonal antibodies, Infect. Immun. 59:1251–1254.

    PubMed  CAS  Google Scholar 

  244. Cryz, S. J., Jr., Hirer, E., Que, J. U., Sadoff, J. C., Brenner, M., and Schaad, U. B., 1991, Clinical evaluation of an octavalent Pseudomonas aeruginosa conjugate vaccine in plasma donors and in bone marrow transplants and cystic fibrosis patients, Antibiot. Chemother. 44: 157–162.

    PubMed  Google Scholar 

  245. Winnie, G. B., Cowan, R. G., and Wade, N. A., 1989, Intravenous immune globulin treatment of pulmonary exacerbations in cystic fibrosis, J. Pediatr. 114:309–314.

    Article  PubMed  CAS  Google Scholar 

  246. Van Wye, J. E., Collins, M. S., Baylor, M., Pennington, J. E., Hsu, Y.-P., Sampanvejsopa, V., and Moss, R. B., 1990, Pseudomonas hyperimmune globulin passive immunotherapy for pulmonary exacerbations in cystic fibrosis, Pediatr. Pulmonol. 9:7–18.

    Article  PubMed  Google Scholar 

  247. Winnie, G. B., and Cowan, R. G., Respiratory tract colonization with Pseudomonas aeruginosa in cystic fibrosis: Correlation between anti-Pseudomonas aeruginosa antibody levels and pulmonary function, Pediatr. Pulmonol. 10:92–100.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Hygiene and Environmental Hygiene, Hygiene-Institut, University of Tübingen, D-7400, Tübingen, Germany

    Gerd Döring

Authors
  1. Gerd Döring
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Pisa, Pisa, Italy

    Mario Campa  & Mauro Bendinelli  & 

  2. University of South Florida, Tampa, Florida, USA

    Herman Friedman

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media New York

About this chapter

Cite this chapter

Döring, G. (1993). Chronic Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis Patients. In: Campa, M., Bendinelli, M., Friedman, H. (eds) Pseudomonas aeruginosa as an Opportunistic Pathogen. Infectious Agents and Pathogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3036-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-3036-7_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6324-8

  • Online ISBN: 978-1-4615-3036-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation