# Trypanosoma cruzi dormancy and its implications for therapeutic treatment

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $477,009

## Abstract

Project Summary/Abstract
 Microbial dormancy, defined as a state of reduced metabolic activity, is well recognized in bacterial systems as a
mechanism of transient resistance to environmental stresses, including antibiotic treatment. We have recently reported
that Trypanosoma cruzi, the agent of Chagas disease, resists long-term exposure to highly cytotoxic compounds due to
the ability of a subpopulation of intracelllular amastigotes to spontaneously assume a dormant state. This new
understanding of T. cruzi biology has implications for how currently available drugs are delivered and how new
compounds capable of reversing dormancy, may be identified. In this application, we propose experiments that will
define the timeframe and limits of T. cruzi dormancy in vivo, among different parasite isolates, if different host tissues
and with respect to the chronicity of the infections. The immunological implications of dormancy will be investigated
and this parasitological and immunological information will be integrated to enhance treatment efficacy using currently
available drugs. Using a novel high content imaging screen, we will identify small molecules that prevent or reverse
dormancy and/or drive the stage conversion of both dormant and actively replicating amastigotes into trypomastigotes.
These compounds will serve as research tools to investigate the molecular pathways involved in dormancy and will be
preliminarily investigated as new therapeutic entities for Chagas disease. We believe that the observation of dormancy
in T. cruzi and the demonstration of its clear role in drug treatment failure is a game changer for treatment design and
drug discovery in T. cruzi. The work in this proposal charts a way forward for therapy for Chagas disease, using new
tools to increase our understanding of the complex set of interacting forces that determine treatment outcomes, and
integrating this information to better use current drugs and discover of new ones.

## Key facts

- **NIH application ID:** 9946936
- **Project number:** 1R01AI151148-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Rick L Tarleton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $477,009
- **Award type:** 1
- **Project period:** 2020-03-10 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9946936

## Citation

> US National Institutes of Health, RePORTER application 9946936, Trypanosoma cruzi dormancy and its implications for therapeutic treatment (1R01AI151148-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9946936. Licensed CC0.

---

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