Genetic Approaches to Study Pseudomonas Aeruginosa Protein Antigens
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.
KeywordsPseudomonas Aeruginosa Parent Strain Genetic Approach Alkaline Protease Passive Immunization
nicotinamide adenine dinucleotide
cross reactive antigen.
Unable to display preview. Download preview PDF.
- 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.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.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.Google Scholar
- Liu, P. V., 1974, Extracellular toxins of Pseudomonas aeruginosa, J. Infect. Dis., 130: 594.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
- 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
- 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.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.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