Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI025669-01
Application #
3139190
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Hamood, A N; Ohman, D E; West, S E et al. (1992) Isolation and characterization of toxin A excretion-deficient mutants of Pseudomonas aeruginosa PAO1. Infect Immun 60:510-7
Frank, D W; Iglewski, B H (1991) Cloning and sequence analysis of a trans-regulatory locus required for exoenzyme S synthesis in Pseudomonas aeruginosa. J Bacteriol 173:6460-8
Storey, D G; Raivio, T L; Frank, D W et al. (1991) Effect of regB on expression from the P1 and P2 promoters of the Pseudomonas aeruginosa regAB operon. J Bacteriol 173:6088-94
Mohr, C D; Rust, L; Albus, A M et al. (1990) Expression patterns of genes encoding elastase and controlling mucoidy: co-ordinate regulation of two virulence factors in Pseudomonas aeruginosa isolates from cystic fibrosis. Mol Microbiol 4:2103-10
Hamood, A N; Wick, M J; Iglewski, B H (1990) Secretion of toxin A from Pseudomonas aeruginosa PAO1, PAK, and PA103 by Escherichia coli. Infect Immun 58:1133-40
Hamood, A N; Iglewski, B H (1990) Expression of the Pseudomonas aeruginosa toxA positive regulatory gene (regA) in Escherichia coli. J Bacteriol 172:589-94
Wick, M J; Frank, D W; Storey, D G et al. (1990) Identification of regB, a gene required for optimal exotoxin A yields in Pseudomonas aeruginosa. Mol Microbiol 4:489-97
Storey, D G; Frank, D W; Farinha, M A et al. (1990) Multiple promoters control the regulation of the Pseudomonas aeruginosa regA gene. Mol Microbiol 4:499-503
Wick, M J; Hamood, A N; Iglewski, B H (1990) Analysis of the structure-function relationship of Pseudomonas aeruginosa exotoxin A. Mol Microbiol 4:527-35
Frank, D W; Storey, D G; Hindahl, M S et al. (1989) Differential regulation by iron of regA and toxA transcript accumulation in Pseudomonas aeruginosa. J Bacteriol 171:5304-13

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