# DETERMINANTS OF VIRULENCE IN GROUP A STREPTOCOCCI

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 1992 · $194,648

## Abstract

Group A streptococcal infections and their sequelae have occurred with a
striking increase in rate and severity in the United States during the
past five years. There have been suggestions that increased virulence in
strains associated with severe infections is due to the appearance of
strains producing increased amounts of certain extracellular toxins. The
purpose of this research is to investigate the contribution to virulence
of several group A streptococcal extracellular product determinants,
specifically genes encoding  erythrogenic toxin A, erythrogenic toxin B
(proteinase), and streptokinase, and characterize the regulatory factors
which control these genes. The specific aims of this study are to: 1.
Elucidate in molecular detail the mechanism of toxigenic conversion by
which group A streptococci produce erythrogenic toxin A, and evaluate
the presence and regulation of expression of this toxin gene in strains
associated with severe diseases such as toxic shock-like syndrome,
bacteremia, and rheumatic fever. 2. Perform a molecular epidemiological
analysis of the erythrogenic toxin B/streptococcal proteinase precursor
gene among different M serotypes and establish whether heterogeneity
accounts for possible differences in proteinase activity and its role in
virulence. 3. Identify and characterize regulatory factors controlling
expression of extracellular product genes such as erythrogenic toxins,
streptolysin O, and streptokinase, and determine whether they are
coordinately regulated. The necessary tools have been developed to
permit a molecular characterization of group A streptococcal virulence.
This proposal has been designed to assess the role of extracellular
products in strains associated with severe infections. Additionally,
experiments are described to characterize the molecular mechanisms
governing the regulation of these extracellular virulence factors. This
information is essential for our understanding of the events that occur
during the pathogenesis of streptococcal disease such as severe systemic
infections, rheumatic fever, and acute glomerulonephritis.

## Key facts

- **NIH application ID:** 3128665
- **Project number:** 2R01AI019304-08A1
- **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:** 1992
- **Award amount:** $194,648
- **Award type:** 2
- **Project period:** 1982-09-15 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128665

## Citation

> US National Institutes of Health, RePORTER application 3128665, DETERMINANTS OF VIRULENCE IN GROUP A STREPTOCOCCI (2R01AI019304-08A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128665. Licensed CC0.

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