Group B streptococci(GBS) are a major cause of serious morbidity and mortality in neonates, pregnant females and other immunocompromised hosts. In previous studies we have shown that fibronectin(FN) enhances phagocytic uptake of antibody coated GBS and offers protective activity against these organisms in a neonatal rat model. The present investigations will examine the mechanism of FN's effect by determining if the cell binding amino acid sequence RGDS of the molecule is responsible for this effect. These will be the first studies on the role of this tetrapeptide in protection against a microbial pathogen and the first to examine its role in vivo. We believe that optimal immunotherapy of neonatal GBS disease may involve the administration of FN or a multivalent RGDS ligand along with antibody to the group B streptococcus. We have described an enzymatic activity on the majority of strains of GBS that inactivates the chemotactic activity of the major chemoattractant derived from the complement system, C5a. The GBS C5a-ase cleaves a 7 residue, approximately 650 kD fragment from the carboxy terminal of the molecule which prevents it from binding to phagocytic cells. We plan to purify this enzyme to homogeneity, produce polyclonal and monoclonal antibodies to it and examine its role in the inflammatory response to GBS infection in an animal model. characterized enzyme that inactivates C5a clearly has the, A purified potential for additional experimental and therapeutic applications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013150-16
Application #
3125398
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1977-01-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
16
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Takahashi, S; Adderson, E E; Nagano, Y et al. (1998) Identification of a highly encapsulated, genetically related group of invasive type III group B streptococci. J Infect Dis 177:1116-9
Bohnsack, J F; Widjaja, K; Ghazizadeh, S et al. (1997) A role for C5 and C5a-ase in the acute neutrophil response to group B streptococcal infections. J Infect Dis 175:847-55

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