Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure

  1. Fernando J Sánchez-Valdéz
  2. Angel Padilla
  3. Wei Wang
  4. Dylan Orr
  5. Rick L Tarleton  Is a corresponding author
  1. University of Georgia, United States

Abstract

The ability of the Chagas disease agent Trypanosoma cruzi to resist extended in vivo exposure to highly effective trypanocidal compounds prompted us to explore the potential for dormancy and its contribution to failed drug treatments in this infection. We document the development of non-proliferating intracellular amastigotes in vivo and in vitro in the absence of drug treatment. Non-proliferative amastigotes ultimately converted to trypomastigotes and established infections in new host cells. Most significantly, dormant amastigotes were uniquely resistant to extended drug treatment in vivo and in vitro and could re-establish a flourishing infection after as many as 30 days of drug exposure. These results demonstrate a dormancy state in T. cruzi that accounts for the failure of highly cytotoxic compounds to completely resolve the infection. The ability of T. cruzi to establish dormancy throws into question current methods for identifying curative drugs but also suggests alternative therapeutic approaches.

Article and author information

Author details

  1. Fernando J Sánchez-Valdéz

    Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Angel Padilla

    Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wei Wang

    Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Dylan Orr

    Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rick L Tarleton

    Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, United States
    For correspondence
    tarleton@uga.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9589-5243

Funding

National Institutes of Health (AI108265)

  • Rick L Tarleton

National Institutes of Health (AI124692)

  • Rick L Tarleton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol A2015 05-010-R3 approved by the University of Georgia Institutional Animal Care and Use Committee under Animal Welfare Assurance #A3437-01.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: December 2, 2017
  2. Accepted: March 25, 2018
  3. Accepted Manuscript published: March 26, 2018 (version 1)
  4. Version of Record published: April 18, 2018 (version 2)

Copyright

© 2018, Sánchez-Valdéz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Fernando J Sánchez-Valdéz
  2. Angel Padilla
  3. Wei Wang
  4. Dylan Orr
  5. Rick L Tarleton
(2018)
Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure
eLife 7:e34039.
https://doi.org/10.7554/eLife.34039

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