Skip to main content

Genetic Approaches to Study Pseudomonas Aeruginosa Protein Antigens

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 185))

Abstract

Pseudomonas aeruginosa produces a large number of extracellular products which may play a role in pathogenesis. We have used genetic techniques to elucidate the relative contribution of these proteins to virulence, and as a method of producing safe toxoids. A mutant has been isolated which produces an immunologically reactive nontoxic form of toxin A, the most toxic extracellular protein produced by P. aeruginosa. Although there are difficulties in production of sufficient quantities of this CRM toxoid, these are likely to be solved by further genetic manipulation. Protection studies with toxin A antibody and studies of mutants deficient in toxin A have confirmed that toxin A plays a role in pathogenesis while clearly showing that toxin A alone cannot totally account for the virulence of P. aeruginosa. Studies of mutants specifically altered in three other products, exoenzyme S, and the two major proteases of P. aeruginosa, elastase and alkaline protease, have clarified the contribution of these products to virulence. Demonstration by genetic studies that exoenzyme S was a major factor in the virulence for one P. aeruginosa strain allowed us to correctly predict that antibody to this product would be protective against infection with that strain.

This work was supported in part by grant DAMD 17-83-G-9556 from the United States Army and AI 14671 from the National Institute of Allergy and Infectious Disease. TIN was supported by a fellowship from the Natural Sciences and Engineering Research Council of Canada.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

ADP:

adenosine 5′-diphosphate

NAD:

nicotinamide adenine dinucleotide

CRM:

cross reactive antigen.

References

  • Bjorn, M. J., Iglewski, B. H., Ives, S. K., Sadoff, J. C. and Vasil, M. L., 1978, Effect of iron on yields of exotoxin A in cultures of Pseudomonas aeruginosa PA103, Infect. Immun 19: 785.

    PubMed  CAS  Google Scholar 

  • Callahan, L. T. III, Martinez, D., Marburg, S., Tolman, R. L. and Galloway, D. R., 1984, Toxoids of Pseudomonas aeruginosa exotoxin A: Photo-affinity inactivation of purified toxin and purified toxin derivatives, Infect. Immun, 43: 1019.

    PubMed  CAS  Google Scholar 

  • Cryz, S. J., and Iglewski, B. H., 1983, Toxoids of Pseudomonas aeruginosa toxin A: production by chemical and genetic means, Rev. Infect. Dis, 5: S992.

    Article  PubMed  CAS  Google Scholar 

  • Cryz, S. J., Freidman, R. L. and Iglewski, B. H., 1980, Isolation and characterization of a Pseudomonas aeruginosa mutant producing a non-toxic, immunologically crossreactive toxin A protein, Proc. Natl. Acad. Sci. U.S.A, 77: 7199.

    Article  PubMed  CAS  Google Scholar 

  • Cryz, S. J., Freidman, R. L., Pavloskis, O. R. and Iglewski, B. H., 1981, Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A:biological, chemical, and immunochemical studies, Infect. Immun, 32: 759.

    PubMed  CAS  Google Scholar 

  • Cryz, S. J., Furer, E., and Germanier, R. 1983a, Passive protection against Pseudomonas aeruginosa infection in an experimental leukopenic mouse model, Infect. Immun, 40: 659.

    PubMed  Google Scholar 

  • Cryz, S. J., Furer, E., and Germanier, R. 1983b, Protection against Pseudomonas aeruginosa infection in a murine burn wound sepsis model by passive transfer of antitoxin A, antielastase, and antilipopolysaccharide, Infect. Immun, 39: 1072.

    PubMed  CAS  Google Scholar 

  • Gray, G. L., Smith, D. H., Baldridge, J. S., Harkins, R. N., Vasil, M. L., Ellson, Y., and Heynecker, H. L., 1984, Cloning, nucleotide sequencing and expression in E. coli of the exotoxin A structural gene of Pseudomonas aeruginosa,Proc. Nat. Acad. Sci., (in press).

    Google Scholar 

  • Doring, G., Obernesser, H. J. and Bozenhart, K., 1981, Extracellular toxins of P. aeruginosa II. Effect of two proteases on human immunoglobulins IgG, IgM and secretory IgA, Zbl. Bakt. Hyg. Mikrobiol, 249: 89.

    CAS  Google Scholar 

  • Howe, T. R. and Iglewski, B. H., 1984, Isolation and characterization of alkaline protease deficient mutants of Pseudomonas aeruginosa in vitro and in a mouse eye model, Infect. Immun, 43: 1058.

    CAS  Google Scholar 

  • Iglewski, B. H. and Kabat D., 1975, NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa exotoxin A, Proc. Natl. Acad. Sci. U.S.A, 72: 2284.

    Article  PubMed  CAS  Google Scholar 

  • Iglewski, B. H., Sadoff J. C., Bjorn, M. J. and Maxwell, E. S., 1978, Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyl- transferase distinct from toxin A, Proc. Natl. Acad. Sci. U.S.A, 75: 3211.

    CAS  Google Scholar 

  • Liu, P. V., 1974, Extracellular toxins of Pseudomonas aeruginosa, J. Infect. Dis., 130: 594.

    Google Scholar 

  • Liu, P. V. and Hsieh, H., 1973. Exotoxins of Pseudomonas aeruginosa III: Characteristics of exotoxin A, J. Infect. Dis, 128: 520.

    Article  PubMed  CAS  Google Scholar 

  • Nicas, T. I. and Iglewski, B. H., 1984a, Isolation and characterization of transposon induced mutants of Pseudomonas aeruginosa deficient in exoenzyme S, Infect. Immun. (in press).

    Google Scholar 

  • Nicas, T. I. and B. H. Iglewski, 1984b, The contribution of exoproducts to virulence of Pseudomonas aeruginosa, Canadian J. Microbiol., (in press).

    Google Scholar 

  • Ohman, D. E., Burns, R. P. and Iglewski, B. H., 1980a, Corneal infections of mice with toxin A and elastase mutants of Pseudomonas aeruginosa, J. Infect. Dis, 142: 547.

    Article  PubMed  CAS  Google Scholar 

  • Ohman, D. E., Cryz, S. J. and Iglewski, B. H., 1980b, Isolation and characterization of a Pseudomonas aeruginosa PAO mutant that produces altered elastase, J. Bacteriol, 142: 836.

    PubMed  CAS  Google Scholar 

  • Ohman, D. E., Sadoff, J. C. and Iglewski, B. H., 1980c, Toxin A deficient mutants of Pseudomonas aeruginosa PA103: Isolation and characterization, Infect. Immun, 28: 899.

    PubMed  CAS  Google Scholar 

  • Pavlovskis, O. R., Pollack, M., Callahan, L. T. III and Iglewski, B. H., 1977, Passive protection by antitoxin in experimental Pseudomonas aeruginosa burn infections, Infect. Immun 18: 596.

    PubMed  CAS  Google Scholar 

  • Pavlovskis, O. R., Edman, D. C., Leppla, S. H., Wretlind, B., Lewis, L. and Martin, K. E., 1981, Protection against experimental Pseudomonas aeruginosa infection in mice by active immunization with toxin A, Infect. Immun 24: 181.

    Google Scholar 

  • Pollack, M. and Prescott, R. K., 1982, Toxoid from exotoxin A of Pseudomonas aeruginosa: preparation and characterization, J. Infect. Dis, 145: 688.

    Article  PubMed  CAS  Google Scholar 

  • Snell, K., Holder, I. A., Leppla, S. H. and Saelinger, C. B., 1978, Role of exotoxin A and protease as possible virulence factors in experimental infections with Pseudomonas aeruginosa, Infect. Immun, 19: 839.

    CAS  Google Scholar 

  • Sokol, P. A., Iglewski, B. H., Hager, T. A., Sadoff, J. C., Cross, A. S., McManus, A., Farber, B. F., and Iglewski, W. F., 1981, Production of exoenzyme S by clinical isolates of Pseudomonas aeruginosa, Infect. Immun, 34: 147.

    CAS  Google Scholar 

  • Sokol, P. A., Cox, C. D., and Iglewski, B. H., 1982, Pseudomonas aeruginosa mutants altered in their sensitivity to the effect of iron on toxin A or elastase yields. J. Bacteriol 151: 783.

    PubMed  CAS  Google Scholar 

  • Vasil, D. E., Kabat, D. and Iglewski, B. H., 1977, Structure activity relationships of an exotoxin of Pseudomonas aeruginosa, Infect. Immun, 16: 353.

    PubMed  CAS  Google Scholar 

  • Walker, H. C., McCleod, G. C., Leppla, S. H., Wretlind, B. and Mason, A. D., 1979, Evaluation of Pseudomonas aeruginosa toxin A in experimental rat burn wound specis, Infect. Immun, 25: 828.

    PubMed  CAS  Google Scholar 

  • Woods, D. E., and Iglewski, B. H., 1983, Toxins of Pseudomonas aeruginosa: new perspectives, Rev. Infect. Dis, 5: S715.

    Article  PubMed  Google Scholar 

  • Wretlind, B. and Pavlovskis, O. R., 1983, Pseudomonas aeruginosa proteases and their role in Pseudomonas infections, Rev. Infect. Dis. 5: S998.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Plenum Press, New York

About this chapter

Cite this chapter

Nicas, T.I., Iglewski, B.H. (1985). Genetic Approaches to Study Pseudomonas Aeruginosa Protein Antigens. In: Atassi, M.Z., Bachrach, H.L. (eds) Immunobiology of Proteins and Peptides—III. Advances in Experimental Medicine and Biology, vol 185. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7974-4_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-7974-4_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-7976-8

  • Online ISBN: 978-1-4684-7974-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics