# Determinants of Streptococcus pyogenes virulence in the primate oropharynx: A genome-wide analysis

> **NIH NIH R21** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2020 · $201,875

## Abstract

PROJECT SUMMARY
The human bacterial pathogen Streptococcus pyogenes (group A streptococcus, GAS) causes more than 600
million cases of pharyngitis annually worldwide. The proposed research seeks to discover, on a genome-wide
scale, GAS genes required for, or contributing to, pharyngitis, the dominant human disease caused by this
pathogen. The pathogen genes and basic molecular pathogenesis processes contributing to the three phases
of pharyngitis: initial colonization, acute clinical disease, and persistence in the oropharynx remain poorly
understood. This basic science knowledge deficit has severely limited the ability to create new clinical tools such
as a successful GAS vaccine. Thus, the studies are designed to address this critical knowledge deficit. We will
combine our very recent success in applying transposon-directed insertion site sequencing (TraDIS) technology
to GAS with our 18 years of productive experience with a cynomolgus macaque model of pharyngitis, currently
the gold standard experimental model for this disease. We will use TraDIS to conduct an in vivo genome-wide
screen that will systematically identify GAS genes required for colonization, clinical disease and persistence in
the oropharynx of cynomolgus macaques. The goal of the proposed studies is to identify new molecular
mechanisms used by GAS to survive in the primate oropharynx. The results of our studies may ultimately help
in formulating novel translational strategies to prevent or treat GAS pharyngitis. To achieve our goals, the
following two specific aims are proposed: Specific Aim 1: Exploit TraDIS for genome-wide identification of GAS
genes required for colonization, acute clinical infection, and persistence (i.e., fitness) in the oropharynx of
cynomolgus macaques. Specific Aim 2: Use isogenic gene-knockout mutant strains to validate the importance
of two selected candidate genes to GAS pharyngitis identified by the genome-wide screen. The proposed line of
research will exploit our innovative and successful application of TraDIS to GAS. It will be the first use of TraDIS
in non-human primates and the first study to investigate determinants of GAS virulence in the oropharynx using
genome-wide transposon mutagenesis.

## Key facts

- **NIH application ID:** 9873918
- **Project number:** 5R21AI139369-02
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** James MALLORY Musser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873918

## Citation

> US National Institutes of Health, RePORTER application 9873918, Determinants of Streptococcus pyogenes virulence in the primate oropharynx: A genome-wide analysis (5R21AI139369-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9873918. Licensed CC0.

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