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. 1982 Jun;36(3):1223–1228. doi: 10.1128/iai.36.3.1223-1228.1982

Contribution of toxin A and elastase to virulence of Pseudomonas aeruginosa in chronic lung infections of rats.

D E Woods, S J Cryz, R L Friedman, B H Iglewski
PMCID: PMC551460  PMID: 6807846

Abstract

A chronic pulmonary infection model in rats was employed to assess the role of individual Pseudomonas aeruginosa exoproducts in disease due to this organism. Groups of rats were inoculated transtracheally with agar beads in which were embedded approximately 10(4) colony-forming units of P. aerugijnosa PAO and the PAO derivatives PR1, T1, E64, and a mixture of T1 and E64 in equal numbers (10(4)). Eight animals from each group were sacrificed at 3, 9, and 30 days after challenge, and their lungs were examined for histopathological changes, bacterial numbers, and the presence of P. aeruginosa exoproducts. The Tox- mutant T1 and the PR1 mutant, which produces enzymatically inactive toxin A, were both found to be less virulent in the rat lung model than was the toxigenic parental strain PAO. Pathological changes seen in animals infected with these mutants were restricted to intra- and peribronchial inflammation, whereas the toxigenic parental strain caused parenchymal changes, including a dense mononuclear-cell infiltration in the alveolar spaces in addition to intra- and peribronchial inflammation. Additionally, mutant E64, which produces a temperature-sensitive elastase, was also found to be less virulent in the rat lung model than was the parental strain. These data demonstrate that both active toxin A and elastase are required for maximum virulence of P. aeruginosa in this model.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bjorn M. J., Vasil M. L., Sadoff J. C., Iglewski B. H. Incidence of exotoxin production by Pseudomonas species. Infect Immun. 1977 Apr;16(1):362–366. doi: 10.1128/iai.16.1.362-366.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowman B. H., Lankford B. J., Fuller G. M., Carson S. D., Kurosky A., Barnett D. R. Cystic fibrosis: the ciliary inhibitor is a small polypeptide associated with immunoglobulin G. Biochem Biophys Res Commun. 1975 Jun 16;64(4):1310–1315. doi: 10.1016/0006-291x(75)90835-9. [DOI] [PubMed] [Google Scholar]
  3. Cash H. A., Woods D. E., McCullough B., Johanson W. G., Jr, Bass J. A. A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am Rev Respir Dis. 1979 Mar;119(3):453–459. doi: 10.1164/arrd.1979.119.3.453. [DOI] [PubMed] [Google Scholar]
  4. Cross A. S., Sadoff J. C., Iglewski B. H., Sokol P. A. Evidence for the role of toxin A in the pathogenesis of infection with Pseudomonas aeruginosa in humans. J Infect Dis. 1980 Oct;142(4):538–546. doi: 10.1093/infdis/142.4.538. [DOI] [PubMed] [Google Scholar]
  5. Cryz S. J., Iglewski B. H. Production of alkaline protease by Pseudomonas aeruginosa. J Clin Microbiol. 1980 Jul;12(1):131–133. doi: 10.1128/jcm.12.1.131-133.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cryz S. J., Jr, Friedman R. L., Iglewski B. H. Isolation and characterization of a Pseudomonas aeruginosa mutant producing a nontoxic, immunologically crossreactive toxin A protein. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7199–7203. doi: 10.1073/pnas.77.12.7199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holloway B. W., Krishnapillai V., Morgan A. F. Chromosomal genetics of Pseudomonas. Microbiol Rev. 1979 Mar;43(1):73–102. doi: 10.1128/mr.43.1.73-102.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Iglewski B. H., Sadoff J. C. Toxin inhibitors of protein synthesis: production, purification, and assay of Pseudomonas aeruginosa toxin A. Methods Enzymol. 1979;60:780–793. doi: 10.1016/s0076-6879(79)60071-x. [DOI] [PubMed] [Google Scholar]
  9. Klinger J. D., Straus D. C., Hilton C. B., Bass J. A. Antibodies to proteases and exotoxin A of Pseudomonas aeruginosa in patients with cystic fibrosis: Demonstration by radioimmunoassay. J Infect Dis. 1978 Jul;138(1):49–48. doi: 10.1093/infdis/138.1.49. [DOI] [PubMed] [Google Scholar]
  10. Liu P. V. Extracellular toxins of Pseudomonas aeruginosa. J Infect Dis. 1974 Nov;130 (Suppl)(0):S94–S99. doi: 10.1093/infdis/130.supplement.s94. [DOI] [PubMed] [Google Scholar]
  11. Liu P. V., Hsieh H. Exotoxins of Pseudomonas aeruginosa. 3. Characteristics of antitoxin A. J Infect Dis. 1973 Oct;128(4):520–526. doi: 10.1093/infdis/128.4.520. [DOI] [PubMed] [Google Scholar]
  12. MORIHARA K., TSUZUKI H., OKA T., INOUE H., EBATA M. PSEUDOMONAS AERUGINOSA ELASTASE. ISOLATION, CRYSTALLIZATION, AND PRELIMINARY CHARACTERIZATION. J Biol Chem. 1965 Aug;240:3295–3304. [PubMed] [Google Scholar]
  13. Ohman D. E., Burns R. P., Iglewski B. H. Corneal infections in mice with toxin A and elastase mutants of Pseudomonas aeruginosa. J Infect Dis. 1980 Oct;142(4):547–555. doi: 10.1093/infdis/142.4.547. [DOI] [PubMed] [Google Scholar]
  14. Ohman D. E., Cryz S. J., Iglewski B. H. Isolation and characterization of Pseudomonas aeruginosa PAO mutant that produces altered elastase. J Bacteriol. 1980 Jun;142(3):836–842. doi: 10.1128/jb.142.3.836-842.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohman D. E., Sadoff J. C., Iglewski B. H. Toxin A-deficient mutants of Pseudomonas aeruginosa PA103: isolation and characterization. Infect Immun. 1980 Jun;28(3):899–908. doi: 10.1128/iai.28.3.899-908.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pavlovskis O. R., Pollack M., Callahan L. T., 3rd, Iglewski B. H. Passive protection by antitoxin in experimental Pseudomonas aeruginosa burn infections. Infect Immun. 1977 Dec;18(3):596–602. doi: 10.1128/iai.18.3.596-602.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pollack M., Callahan L. T., 3rd, Taylor N. S. Neutralizing antibody to Pseudomonas aeruginosa exotoxin in human sera: evidence for in vivo toxin production during infection. Infect Immun. 1976 Oct;14(4):942–947. doi: 10.1128/iai.14.4.942-947.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pollack M., Taylor N. S., Callahan L. T., 3rd Exotoxin production by clinical isolates of pseudomonas aeruginosa. Infect Immun. 1977 Mar;15(3):776–780. doi: 10.1128/iai.15.3.776-780.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stevens R. M., Teres D., Skillman J. J., Feingold D. S. Pneumonia in an intensive care unit. A 30-month experience. Arch Intern Med. 1974 Jul;134(1):106–111. [PubMed] [Google Scholar]
  20. Thomassen M. J., Boxerbaum B., Demko C. A., Kuchenbrod P. J., Dearborn D. G., Wood R. E. Inhibitory effect of cystic fibrosis serum on pseudomonas phagocytosis by rabbit and human alveolar macrophages. Pediatr Res. 1979 Sep;13(9):1085–1088. doi: 10.1203/00006450-197909000-00030. [DOI] [PubMed] [Google Scholar]
  21. Vasil M. L., Iglewski B. H. Comparative toxicities of diphtherial toxin and Pseudomonas aeruginosa exotoxin A: evidence for different cell receptors. J Gen Microbiol. 1978 Oct;108(2):333–337. doi: 10.1099/00221287-108-2-333. [DOI] [PubMed] [Google Scholar]
  22. Wood R. E. Pseudomonas: the compromised host. Hosp Pract. 1976 Aug;11(8):91–100. doi: 10.1080/21548331.1976.11706983. [DOI] [PubMed] [Google Scholar]
  23. Wretlind B., Wadström T. Purification and properties of a protease with elastase activity from Pseudomonas aeruginosa. J Gen Microbiol. 1977 Dec;103(2):319–327. doi: 10.1099/00221287-103-2-319. [DOI] [PubMed] [Google Scholar]

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