# Deciphering the Role of Rgg in the Pneumococcal Signaling, Colonization and Virulence Portfolio

> **NIH NIH R01** · CARNEGIE-MELLON UNIVERSITY · 2021 · $90,532

## Abstract

Project Summary
The overall goal of this project is to advance our understanding of pneumococcal colonization.
Pneumococcal diseases are major causes of morbidity and mortality in the United States and worldwide,
and colonization of the nasopharynx is the first step for pneumococcal infections. While much is known
about phenotypes and cellular processes associated with pneumococcal colonization, the molecules
coordinating these processes are not well understood. Our preliminary work characterizing the Rgg144-
Shp144 regulator-peptide signal transduction system has lead us to hypothesize that this system plays a
pivotal role in orchestrating pneumococcal colonization. At a broad level, our work will provide insight into
pneumococcal colonization and the Rgg family of signal transduction systems, widely distributed in
streptococci and enterococci. At a specific level, we will determine which colonization-associated
phenotypes are regulated by Rgg144 and establish whether Rgg144 mediates these phenotypes via
regulation of the capsule (Aim 1). We will to identify specific residues associated with peptide-regulator
interactions and with regulator-DNA interactions (Aim 2). We will reveal SHP144-derived peptides that act
as agonists and antagonists in vitro and in vivo, for use in manipulating the system in basic functional
studies as well as future drug development efforts (Aim 2 and 3). We will provide an in vivo
characterization of Rgg144 expression and activity in multiple tissues over time using two different murine
models of pneumococcal infection (Aim 3). Together, our findings will uncover the contribution of Rgg144
to transcriptional regulation of the capsule, advance our understanding of pneumococcal colonization,
and shed light on the development of anti-pneumococcal therapies. The work is innovative in that it
approaches the study of Rggs by generating a spatio-temporal map of Rgg144 expression and activity
during infection.

## Key facts

- **NIH application ID:** 10448064
- **Project number:** 3R01AI139077-03S1
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** Natalia Luisa Hiller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $90,532
- **Award type:** 3
- **Project period:** 2019-05-23 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448064

## Citation

> US National Institutes of Health, RePORTER application 10448064, Deciphering the Role of Rgg in the Pneumococcal Signaling, Colonization and Virulence Portfolio (3R01AI139077-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10448064. Licensed CC0.

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