Pseudomonas aeruginosa is a major cause of severe opportunistic infections and of chronic infections in children with cystic fibrosis. lt is difficult to treat with available antibiotics and currently no effective vaccine is available. The pathogenesis of P. aeruginosa infections is not completely understood. However, it is clear that virulence of this bacterium is multifactorial. Recent evidence suggests that exoenzyme S is a significant virulence factor of P. aeruginosa and suggests that S antibodies are protective. The long-term goal of this research is to determine the role of exoenzyme S in the pathogenesis of P. aeruginosa infections. The research proposed utilizes immunological, genetic and recombinant DNA methods in order to: explore the protective capacity of exoenzyme S specific antibodies; increase our understanding of exoenzyme S genetics, and extend our knowledge about the contribution of exoenzyme S to virulence of P. aeruginosa. The specific aims of this proposal are: (1) to evaluate the protective capacity of exoenzyme S antibodies in burned mice infected with P. aeruginosa: (2) to quantitate human antibody to exoenzyme S: (3) to subclone and characterize the exoenzyme S gene on pDF102, and (4) to extend our genetic studies to include additional exoenzyme mutants in other P. aeruginosa strain and in other exoenzyme S genes.