MECHANISMS OF HOST RESISTANCE OF GROUP B STREPTOCOCCI

NIH RePORTER · NIH · R01 · $111,191 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
3125391
Project number
2R01AI013150-14
Recipient
UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
SAM.gov UEI
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Principal Investigator
HARRY R HILL
Activity code
R01
Funding institute
NIH
Fiscal year
1991
Award amount
$111,191
Award type
2
Project period
1977-01-01 → 1994-11-30