Evidence of a role for permeability factors in the pathogenesis of salmonellosis.

Two clinical isolates of Salmonella typhimurium were shown to produce two skin permeability factors. One factor was heat stable and rapid in onset while the other was heat labile and elicited maximal induration by 18 to 24 hr. The rapid, erythematous permeability factor (PF) response could not be prevented by antisera to cholera toxin or Salmonella antisomatic serum, but it could be simulated by high concentrations of lipopolysaccharide from S. typhimurium. The appearance of the delayed PF reaction was indistinguishable from that of purified cholera toxin. Histological comparisons of rabbit skin injected with Salmonella-delayed PF and cholera toxin revealed that both toxins resulted in gross edema and infiltration of polymorphonuclear leukocytes after 18 hr. The Salmonella-delayed PF was shown to be resistant to a variety of enzymes, sensitive to extremes in pH, and had an isoelectric point of pH 4.8. Unlike Salmonella lipopolysaccharide skin activity, the Salmonella-delayed PF was destroyed at 100 C and was neutralized by monospecific cholera antitoxin. The Salmonella-delayed PF, which shares antigenic determinants with cholera toxin, appears to be elaborated by living S. typhimurium cells in the rabbit ligated intestine, since rabbits immunized with procholeragenoid were protected against fluid loss from live cell challenge. Finally, production of the rapid PF is a stable genetic trait, while delayed PF production is apparently an unstable characteristic among the salmonellae.