# DETERMINANTS OF VIRULENCE IN GROUP A STREPTOCOCCI

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 1988 · $115,933

## Abstract

The overall goal of this research is to study the determinants of
virulence in beta hemolytic streptococci.  The techniques of
recombinant DNA technology have allowed new approaches to be
taken in the study of these pathogenic orgnaisms.  Specifically,
the multifactorial properties of the organism thought to be
responsible for the disease state can now be individually isolated
and subjected to intense study at the molcular level.  We have
isolated several genes from hemolytic streptococci which produce
extracellular products known to be involved in the initiation of
tissue damage; i.e., erythrogenic toxin, proteinase, streptokinase,
hyaluronidase, and streptolysin O.  The specific amis of this
investgation are to:  1.  Utilize DNA probes from the above
extracellular product genes in hybridization experiments to
determine the presence of these genes in a large number of
streptococcal strains obtained throughout the world, and to
determine whether individual determinants can be linked to
strains associated with a specific disease; e.g., acute
glomerulonephrintis, rheumatic fever, or scarlet fever.  2.
Elucidate the study further the mechanism of toxigenic
conversion by whihc lysogenic strains of S.  poygenes produce the
type A erythrogenic toxin.  3.  Determine whether the type B
erythrogenic toxin and the zymogen precursor of streptococcal
proteinase are the same products, and study the determinants of
these products at the molecular level.  4.  Perform site directed
mutagenesis and protein engineering experiments with the cloned
streptokinase gene in order to study structure function
relationships of this protein and also obtain second generation
streptokinases.  Additionally, study in further detail the group A
streptokinase, which has recently been identified as te nephritis
strain-associated antigen.

These studies should provide information about structure function
relationships of individual gene products, how they regulated,
their distriubtion among streptococci and related organisms, and
further insight into mechanisms of action and role in
pathogenesis.  Specific DNA probes will also be available for
developing reapid detection and identification systems, as well as
the linking of particular determinants to streptococcal strains
associated with specific diseases.  Finally, second generation
streptokinases will be constructed which could have immediate
clinical applicability in thrombolytic therapy.

## Key facts

- **NIH application ID:** 3128667
- **Project number:** 5R01AI019304-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **SAM.gov UEI:** GY8NMUZQXVS7
- **Principal Investigator:** Joseph J Ferretti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $115,933
- **Award type:** 5
- **Project period:** 1982-09-15 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128667

## Citation

> US National Institutes of Health, RePORTER application 3128667, DETERMINANTS OF VIRULENCE IN GROUP A STREPTOCOCCI (5R01AI019304-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128667. Licensed CC0.

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