# Regulation of Francisella virulence by sRNAs

> **NIH NIH R21** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $228,000

## Abstract

PROJECT SUMMARY
Francisella tularensis (Ft) is a potential agent of bioterror, facultative intracellular pathogen and the causative
agent of tularemia. Based on several of its attributes, Ft has been named by the CDC as a Tier 1 agent. While
several advances have been made in the last ~15 years regarding the cell biology of this pathogen, its method
of virulence gene regulation remains incompletely understood. To survive and thrive in often hostile
environments, a bacterium has to monitor its surroundings and adjust its gene expression and physiology
accordingly. This is especially important for pathogenic bacteria that continuously interact with the host during
an infection. Gene regulation is traditionally mediated by protein regulatory factors, but Ft contains few protein
regulatory factors and is devoid of classically arranged two-component regulatory systems, yet mediates
complex host-pathogen processes such as suppression of the immune response early after host contact and
escape from the Francisella-containing vacuole into the cytosol. A limited number of orphan two-component
members exist including the response regulator PmrA. PmrA is a key factor in Francisella pathogenesis, as it
has been demonstrated to regulate Ft biofilm formation, intramacrophage survival and animal virulence. Small
RNAs (sRNAs) are also increasingly associated with the regulation of virulence in pathogens, and we have
identified 661 Ft sRNAs, including the subset regulated by PmrA (n=81). The overall goal of this research is to
understand the transcriptional/post-transcriptional control of virulence in this important pathogen. The overall
objective is to identify virulence-associated sRNAs (PmrA-regulated as well as those differentially expressed
in macrophages). The central hypothesis is that Ft sRNAs are influenced by PmrA and the macrophage
environment to regulate virulence. The achievement of our goals will uncover new targets for Ft vaccines or for
therapeutics to counteract this dangerous pathogen.

## Key facts

- **NIH application ID:** 9893816
- **Project number:** 5R21AI140001-02
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** JOHN S GUNN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 5
- **Project period:** 2019-03-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893816

## Citation

> US National Institutes of Health, RePORTER application 9893816, Regulation of Francisella virulence by sRNAs (5R21AI140001-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893816. Licensed CC0.

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