# GENETIC CONTROL OF VIRULENCE IN GROUP STREPTOCOCCI

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1991 · $123,172

## Abstract

Group A streptococci are still a major cause of illness in
children.  The resurgence of rheumatic fever and associated heart
disease in many communities in the United States in the past two
years has reminded the medical community that this pathogen has
the potential to initiate serious morbidity.  Pathogenic
streptococci are covered with a fibrous protein coat which
permits them to avoid the human immunological defenses.  Like
most bacterial pathogens the macromolecular composition of this
fibrous layer and the capacity to cause disease is finely
regulated and subject to change.  Streptococci switch between
virulent and avirulent states, a phenomenon termed phase
variation.  Understanding the molecular basis of phase variation
and its role in the infectious process is the ultimate goal of
this project.

Virulence is dependent on a multitude of factors, antiphagocytic
M proteins, and inhibitor of chemotaxis, IgG Fc receptor proteins
and a variety of toxins.  Our studies showed that expression of M
protein is under the control of a reversible genetic switch and
that genes which encode these proteins are clustered on the
streptococcal chromosome.  We propose that these genes compose a
complex regulatory circuit which is controlled by a master gene,
the product of the virR locus.  We also suggest that this
regulatory pathway coordinates the "on off" expression of these
three virulence factors.  To test this model the nucleotide
sequence of this gene cluster will be completed.  The virR gene
and its role in coordinating expression and phase variation of
these surface protein genes will be investigated.  The impact of
virR on promoter recognition and transcription of each gene will
be examined by quantitating and sizing mRNA transcripts from each
gene.  Our studies will make use of lacZ gene fusions and
insertion mutagenesis to locate and define components of the
phasing switch.

This project will extend the knowledge of the pathobiology of
group A streptococcal infections and could ultimately explain the
persistence of streptococci in human populations.  Furthermore,
this study will yield a wealth of protein sequence information,
all proteins which contribute to the pathogenic potential of
these bacteria.  This information may be useful for the
development of a subunit, polyvalent vaccine.

## Key facts

- **NIH application ID:** 3126789
- **Project number:** 5R01AI016722-09
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** PAUL Patrick CLEARY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $123,172
- **Award type:** 5
- **Project period:** 1981-09-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126789

## Citation

> US National Institutes of Health, RePORTER application 3126789, GENETIC CONTROL OF VIRULENCE IN GROUP STREPTOCOCCI (5R01AI016722-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126789. Licensed CC0.

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