# New anti-tubercular agents targeting intracellular bacteria

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $935,324

## Abstract

Summary
Tuberculosis remains a major global health burden with ~1.6 million deaths in 2021 and a latently-infected
population of billions. Mycobacterium tuberculosis, the causative agent, is a sophisticated pathogen which can
persist for decades in the human host and which requires lengthy treatment for cure with multiple antibiotics.
One of the features of M. tuberculosis is its ability to survive and replicate inside human cells, including
macrophages, one of the normal host defense mechanisms against infection. Intracellular bacteria are a specific
population which can be hard to kill, in part due to the requirement that molecules enter eukaryotic cells, and in
part due to the different physiological state in which the bacteria persist. Increasing evidence points to a higher
level of antibiotic tolerance in intracellular bacteria, as well as increased heterogeneity.
In order to identify new drugs which can shorten therapy, we focused on the identification of novel anti-tubercular
agents which are active against intracellular bacteria. We identified a number of scaffolds which inhibit
mycobacterial intracellular replication using a high content screen to monitor bacterial and eukaryotic cell survival
simultaneously. From these, we selected high priority series with attractive properties for further evaluation.
The overall aims of this proposal are to (i) evaluate a high priority chemical series with intracellular activity, (ii)
identify the target and mechanism of action of this novel series and (iii) determine the best companion agents
for a new regimen. The major outcome will be a molecule series with a known mechanism of action with in vivo
validation ready for lead optimization.

## Key facts

- **NIH application ID:** 10801211
- **Project number:** 1R01AI173110-01A1
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Tanya Parish
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $935,324
- **Award type:** 1
- **Project period:** 2024-06-21 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801211

## Citation

> US National Institutes of Health, RePORTER application 10801211, New anti-tubercular agents targeting intracellular bacteria (1R01AI173110-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10801211. Licensed CC0.

---

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