# Determinants of Paucibacillary Mtb Infection in Mice

> **NIH NIH U19** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $485,169

## Abstract

Tuberculosis (TB) chemotherapy eliminates disease symptoms, but often fails to sterilize Mycobacterium
tuberculosis (Mtb) leaving apparently cured TB patients at risk of disease relapse. How Mtb survives during post-
treatment persistent infections (PTPI) is ill defined and we lack a full understanding of the immune determinants
that prevent progression to active TB (relapse).
We developed a paucibacillary (low bacterial numbers) mouse model that mimics PTPI in in humans. We found
that silencing of in vivo essential genes cured Mtb infections in mice to the extent that colony forming units (CFU)
were no longer detected on agar plates. However, as in humans, mice were often not sterilized, and
paucibacillary infection resulted in relapse TB. Our model allows us to interrogate both, the mechanisms that
enable Mtb to persist despite host immunity and the host factors that are required to control and sterilize Mtb
infection. We will use this model to (1) compare post-treatment persistent infection (PTPI) in mice and humans
(2) determine the importance of specific leukocyte subsets for the establishment or control of paucibacillary Mtb
infection and (3) identify Mtb genes that are required for paucibacillary persistence.

## Key facts

- **NIH application ID:** 10831006
- **Project number:** 5U19AI162568-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** SABINE EHRT
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $485,169
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831006

## Citation

> US National Institutes of Health, RePORTER application 10831006, Determinants of Paucibacillary Mtb Infection in Mice (5U19AI162568-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10831006. Licensed CC0.

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