# Mtb strain-dependent mechanisms of pathogenesis in mouse models

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2021 · $590,820

## Abstract

Tuberculosis (TB) is a highly heterogeneous human disease that develops in some, but not all,
individuals who inhale 1-3 infectious bacilli of Mycobacterium tuberculosis (Mtb). TB disease can
range from pulmonary disease that is mild and self-resolving, to severe, or can disseminate to
extrapulmonary sites. Understanding the complexity of TB pathogenesis requires a holistic
approach that integrates human and animal model studies. Although there is growing evidence
that Mtb strain-dependent factors drive different infection outcomes, the in vivo mechanisms that
govern these outcomes are poorly understood. In this project, we start with clinical Mtb strains
associated with different pathogenic outcomes (e.g., high transmission or disseminated disease)
or mutant strains harboring modifications in gene candidates, identified in Core A and Project
1, to identify polymorphisms in Mtb strains associated with distinct human clinical outcomes.
Mice infected with these clinical or mutant Mtb strains will be used to investigate how they
govern three distinct stages of pathogenesis: 1) establishing infection at the site of aerosol
inhalation, 2) dissemination to distant sites, and 3) interactions with host immunity in distinct
lung macrophage populations. These studies will leverage our group’s recent advances in
mouse TB models, including identifying the earliest cellular events after aerosol Mtb infection,
tracking Mtb dissemination using a physiologic, ultra low-dose (ULD) infection model in which
mice are infected with 1-3 CFUs of aerosolized Mtb, and assessing paired host and Mtb
transcriptomes in distinct pulmonary macrophage types. Multiparameter confocal microscopy
and advanced quantitative image analysis will be used to determine how these Mtb strain-
dependent factors shape immune cell interactions at infection sites. The overall goal of the
proposed experiments is to gain insight into molecular and cellular mechanisms of pathogenesis
at distinct stages of Mtb infection to inform development of novel host- and pathogen-directed
interventions.

## Key facts

- **NIH application ID:** 10271174
- **Project number:** 1U19AI162583-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** KEVIN B URDAHL
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $590,820
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271174

## Citation

> US National Institutes of Health, RePORTER application 10271174, Mtb strain-dependent mechanisms of pathogenesis in mouse models (1U19AI162583-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10271174. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*