# Investigating the Role of Protease-mediated signaling in M. tuberculosis Virulence

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $229,727

## Abstract

TITLE
Investigating the Role of Protease-mediated signaling in M. tuberculosis Virulence
ABSTRACT
The bacterium M. tuberculosis (Mtb ) persists as a threat to human health, with tuberculosis (TB)
killing an estimated 1-2 million people annually. Unfortunately, a molecular understanding of how
Mtb evades the immune system is lacking. This critical gap in knowledge slows the design of new
therapies that seek to improve TB vaccine efficacy or to promote sterilizing immunity in TB patients.
My hypothesis is that when Mtb infects a host macrophage, it deploys proteases to degrade
proteins involved in the immune response. I propose to explore the hypothesis that secreted Mtb
proteases contribute to virulence by cleaving host proteins. We will use a unique combination of
proteomics methods to 1) identify potential targets of secreted Mtb proteases, and to 2) globally
profile proteolysis events during Mtb infection. I will then use genetic analysis in both M.
tuberculosis and the host to disrupt both the bacterial proteases and their putative host substrates
to evaluate the role that proteolysis plays in TB pathogenesis.

## Key facts

- **NIH application ID:** 10526871
- **Project number:** 1R21AI166450-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Bennett Penn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $229,727
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526871

## Citation

> US National Institutes of Health, RePORTER application 10526871, Investigating the Role of Protease-mediated signaling in M. tuberculosis Virulence (1R21AI166450-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10526871. Licensed CC0.

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