# A Murine Group A Streptococcus Transmission Model for Male-Biased Acute Infection in the Mucosa of the Upper Respiratory Tract

> **NIH NIH R21** · MONTANA STATE UNIVERSITY - BOZEMAN · 2021 · $180,000

## Abstract

Project Summary: The goal of this project is to establish a murine Group A Streptococcus (GAS) transmission
model that leads to acute infection in the mucosa of the upper respiratory tract in recipient mice. GAS is a major
human pathogen that causes common pharyngeal and skin infections. GAS also occasionally causes severe
invasive infections such as pneumonia, necrotizing fasciitis, bacteremia, and toxic shock syndrome. Murine and
nonhuman primate infection models have been valuable for understanding GAS pathogenesis; however, these
models involve high GAS inocula and cannot be used to investigate the onset of pharyngeal GAS infections.
Consequently, there is a significant knowledge gap regarding immune protection and GAS pathogenesis during
the onset of acute pharyngeal GAS infection. Another knowledge gap is the lack of understanding of the basis
for the differential susceptibility to infectious respiratory diseases between males and females. We recently
found that wild-type M1T1 GAS is effectively cleared from the lung in a murine intratracheal pneumonia infection
model but not from the skin with subcutaneous infection and that the clearance of GAS from the lung requires
the gp91Phox (Nox2) gene, which encodes the β chain of the catalytic subunit of the NADPH oxidase. These
findings inspired us to test whether gp91phox knockout (KO) naïve mice develop acute GAS infection in the
nasopharynx and oropharynx after they are comingled with donor mice that were inoculated in the nostrils with
GAS. Pilot tests showed that male but not female gp91phox KO recipient mice acquired acute infection in the
mucosal epithelium of the upper respiratory tract within 6 days after comingling. Based on these exciting and
surprising preliminary results, we propose to establish a Group A Streptococcus transmission model for male-
biased acute infection in the mucosal epithelium of the upper respiratory tract in gp91phox KO recipient mice (Aim
1) and determine the basis for the gender bias in acute Group A Streptococcus infection in the mucosal
epithelium of the upper respiratory tract (Aim 2). The successful execution of this project would provide a novel
GAS transmission model that will be invaluable for investigation of innate immune protection and GAS
pathogenesis during the onset of pharyngeal GAS infections. This project also has the potential to provide a
new paradigm to explain the gender differences in susceptibility to respiratory infections.

## Key facts

- **NIH application ID:** 10171774
- **Project number:** 5R21AI153755-02
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** BENFANG LEI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $180,000
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171774

## Citation

> US National Institutes of Health, RePORTER application 10171774, A Murine Group A Streptococcus Transmission Model for Male-Biased Acute Infection in the Mucosa of the Upper Respiratory Tract (5R21AI153755-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10171774. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*