The Role of Exoenzyme S in Infections with Pseudomonas aeruginosa

Abstract

To define the contribution of exoenzyme S to the pathogenesis of infections with Pseudomonas aeruginosa, we have compared the ability of an exoenzyme S-deficient mutant, 388 exs1::Tn1, and that of its exoenzyme S-producing parent to colonize and disseminate in burned mice infected with this organism. Both the exoenzyme S-deficient mutant and the parent strain proliferated in burned skin, but only the parent strain was able to effectively disseminate to blood and other tissues. The reduced ability of the mutant to disseminate was not due to alterations in serum sensitivity, lipopolysaccharide composition, or motility. The exoenzyme S-deficient mutant was able to disseminate in the presence of the exoenzyme S-producing parent. Antibody to purified exoenzyme S was able to greatly reduce dissemination of the exoenzyme S-producing parent strain but did not prevent colonization in the burned skin. These data suggest that exoenzyme S does not contribute to the initial colonization but does contribute to the establishment of disseminated infection.

The exoenzyme S regulon of Pseudomonas aeruginosa

“…A variety of extracellular products appears to contribute to pathogenicity, including several proteases, cytotoxins, phospholipases, neuraminidase, capsular polysaccharides and lipopolysaccharides. A factor that is associated with the ability of P. aeruginosa to cross epithelial barriers and cause a blood-borne infection is the ADP-ribosyltransferase, exoenzyme S (Nicas and Iglewski, 1985;Nicas et al, 1985a).…”

Cloning and sequence analysis of a trans-regulatory locus required for exoenzyme S synthesis in Pseudomonas aeruginosa

“…One extracellular product, exoenzyme S, appears to be a major virulence determinant involved in the dissemination of P. aeruginosa from the initial site of colonization in the skin to the bloodstream of burned and infected animals (17,19). The ability to disseminate correlates to an increased incidence of fatal sepsis in these animals.…”

“…The ability to disseminate correlates to an increased incidence of fatal sepsis in these animals. Passive administration of antiserum to exoenzyme S protects animals from sepsis but has no significant effect on the numbers of organisms recovered from the site of colonization (17). An exoenzyme S-deficient phenotype also correlates to a reduction in the amount and severity of tissue damage associated with P. aeruginosa chronic lung infections (35,36).…”

Alteration of pulmonary structure by Pseudomonas aeruginosa exoenzyme S

“…In animal model studies comparing infections produced by parental P . aeruginosa strains with those produced by isogeneic mutants, singly deficient in exoenzyme S, it has been shown that infections with exoenzyme S-positive strains are much more severe (Nicas et al, 1985;Woods and Sokol, 1985): Phenotypic analysis of P . aeruginosa strains isolated from pulmonary infections in man showed that these strains produce significantly more exoenzyme S than strains isolated from other clinical sources such as urine or wound infections .…”

“…aeruginosa parent strains and isogeneic mutants singly deficient in either elastase or exoenzyme S. The parent strains were shown to be more virulent (Woods et al, 1982;Blackwood et al, 1983;Nicas et al, 1985;Woods and Sokol, 1985).…”