# Conditional Expression of Mycobacterial Genes

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $547,277

## Abstract

Abstract
People with latent tuberculosis (TB) infection (LTBI) are at risk of developing active disease. TB chemotherapy
often fails to sterilize Mycobacterium tuberculosis (Mtb), leaving individuals at risk of relapse TB. How Mtb
survives during paucibacillary persistent TB infections in humans or in animal models is for the most part
unknown. Drug treatment and silencing of in vivo essential genes can cure acute and chronic Mtb infections in
mice to the extent that CFU can no longer be detected on agar plates. However, as in humans, Mtb in these
mice is often not sterilized, and paucibacillary persistence may eventually result in relapse of TB. We have
established paucibacillary mouse models by infecting mice with mutants conditionally lacking proteins that are
required for in vivo growth and high-titer persistence. We will use conditional knockdown mutants to identify the
metabolic pathways that Mtb requires to establish and maintain paucibacillary persistence in mice. Enzymes that
are required during growth in vivo, during high titer persistence in chronic mouse infection, and are also essential
during paucibacillary persistence represent the most valuable targets. Our work can identify and prioritize them.
We will also investigate the importance of key host immune factors for the control of paucibacillary TB and
investigate the immune responses associated with TB relapse. This project will lead to a deeper understanding
of Mtb’s metabolic adaptations that facilitate paucibacillary persistence in mice, increase understanding of host
immune factors that control paucibacillary Mtb and uncover mechanisms of control or disease progression in TB.

## Key facts

- **NIH application ID:** 10231049
- **Project number:** 5R01AI063446-14
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** SABINE EHRT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $547,277
- **Award type:** 5
- **Project period:** 2006-02-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231049

## Citation

> US National Institutes of Health, RePORTER application 10231049, Conditional Expression of Mycobacterial Genes (5R01AI063446-14). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10231049. Licensed CC0.

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