Chronic Lung Infection Model Research Articles

Studies on the ability of alginate to act as a protective immunogen against infection with Pseudomonas aeruginosa in animals.

Most patients with cystic fibrosis become colonized and infected with mucoid Pseudomonas aeruginosa. The major component of the mucoid material has been identified as the polysaccharide alginic acid. The present work was undertaken to determine whether antibody to alginate is protective in a model of chronic lung infection with P. aeruginosa in rats. Bacterial clearance was associated with a rise in titers of antibody to alginate. In a number of animals a rise in antibody titers was not seen, and in fact a decrease was noted at 30 days compared with 10 days. This observation suggested the possibility of immune complex formation due to antigen excess. Evidence for immune complex deposition in tissues was obtained by immunofluorescence studies. Thus antibody to alginate may offer strain-dependent protection against chronic lung infection with P. aeruginosa in rats; however, immune complex formation should be considered as a possible consequence of immunization with alginate.

The contribution of exoproducts to virulence of Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces a large number of extracellular products which may contribute to its virulence. We have employed a genetic approach to determine the contribution of toxin A, exoenzyme S, elastase and alkaline protease to the pathogenesis of P. aeruginosa. Mutations have been introduced with chemicals or transposons. Mutants have been identified using immunological, chemical, or toxicity assays. Mutants were extensively characterized in vitro to ascertain that they were identical to their parent strain except for the production of the desired product. Appropriate mutants were compared with their parent strains in several animal models: the burned mouse model, the mouse corneal infection model, and a rat model of chronic lung infection. The data indicate that virulence of P. aeruginosa is multifactorial. Further, the relative contribution of a given P. aeruginosa product may vary with the type of infection.

Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections.

Exoenzyme S is an extracellular ADP-ribosyltransferase enzyme produced by Pseudomonas aeruginosa. Mutants of Pseudomonas aeruginosa deficient in this enzyme have been shown to have reduced virulence in infections of burned mice. The contribution of exoenzyme S to the pathogenesis of chronic lung infections with this organism was evaluated by examining the incidence of exoenzyme S production by Pseudomonas aeruginosa strains isolated from cystic fibrosis patients and comparing an exoenzyme S deficient mutant and its exoenzyme S producing parent in a rat chronic lung infection model. Of 51 isolates examined, 43% produced detectable levels of exoenzyme S. While both the exoenzyme S deficient mutant and its parent strain were equally capable of colonizing and persisting in rat lungs, the exoenzyme S producing parent elicited a greater degree of lung damage. These data suggest that exoenzyme S contributes to the pathogenesis of chronic lung infections.

Contribution of exoenzyme S to the virulence of Pseudomonas aeruginosa.

Exoenzyme S is an extracellular ADPR transferase produced by P. aeruginosa. Forms of this enzyme that have thus far been purified are not toxic, however, exoenzyme S clearly contributes to the virulence of strain 388. Thus, a Tn1 mutant deficient in exoenzyme S was found to be markedly less virulent than its exoenzyme S-producing parental strain in both a burned mouse infection model and a rat chronic lung infection model. Exoenzyme S does not appear to contribute to initial colonization of the rat lung or the burned mouse skin. Exoenzyme S does, however, appear to contribute to local tissue damage in the rat lung, and to dissemination of P. aeruginosa from the skin into the blood and distant organs of the burned mouse. Perhaps our most important observation is that specific antibody against exoenzyme S confers a high level of protection against subsequent infection of burned mice. While these results must be extended to include additional strains they are encouraging, and they underscore the relative importance of exoenzyme S in the pathogenesis of P. aeruginosa infections.