# Transcriptome and proteome remodeling by Mycobacterium tuberculosis MazF toxins

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $621,353

## Abstract

Project Summary
Mycobacterium tuberculosis (Mtb) has adapted to survive a wide range of assaults—from our immune response
to antimicrobial therapeutics—intended to eradicate the organism. However, the molecular switches that enable
Mtb to endure these stresses, to slow replication or to become dormant as a latent tuberculosis (TB) infection
are not known. Emerging studies on the molecular underpinnings of stress survival generally point to a major
role for toxin-antitoxin (TA) systems, which are operons comprising adjacent genes encoding two small proteins,
a toxin and its cognate antitoxin that inhibits toxin activity in the TA protein-protein complex. However, several
bottlenecks have impeded progress toward rigorous testing of this provocative association. This proposal enlists
a strong multidisciplinary team with expertise in all core components of the proposed work—RNA-seq, TA
systems, Mtb biology/physiology and bioinformatics/computational biology. The genome-scale approach
developed in the PI’s laboratory, 5’ RNA-seq, will be used to overcome these obstacles as they apply to the
eleven-member MazE (antitoxin) – MazF (toxin) family in Mtb. 5’ RNA-seq will facilitate comprehensive detection
of MazF targets in the Mtb transcriptome under unstressed conditions or after exposure to stresses that are
relevant to latent TB infection. Finally, the impact of MazF toxins on the Mtb proteome will be investigated.
Collectively, these approaches will identify the environmental signals that trigger toxin activation in Mtb, provide
an accurate snapshot of RNAs targeted by MazF toxins under these metabolic states, and reveal clues to how
toxin-mediated RNA cleavage alters Mtb physiology. These goals align well with “Priority 1: Improve
Fundamental Knowledge of TB” of the five components of the NIAID Strategic Plan for Tuberculosis Research
released in September 2018.

## Key facts

- **NIH application ID:** 10738768
- **Project number:** 5R01AI143760-05
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** NANCY ANN WOYCHIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $621,353
- **Award type:** 5
- **Project period:** 2019-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10738768

## Citation

> US National Institutes of Health, RePORTER application 10738768, Transcriptome and proteome remodeling by Mycobacterium tuberculosis MazF toxins (5R01AI143760-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10738768. Licensed CC0.

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