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Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease

Author

Listed:
  • Zongyuan Liu

    (University of Oklahoma
    University of Oklahoma)

  • Rebecca Ulrich vonBargen

    (University of Oklahoma
    University of Oklahoma)

  • April L. Kendricks

    (Southern Star Medical Research Institute)

  • Kate Wheeler

    (University of Oklahoma)

  • Ana Carolina Leão

    (Baylor College of Medicine)

  • Krithivasan Sankaranarayanan

    (University of Oklahoma
    University of Oklahoma)

  • Danya A. Dean

    (University of Oklahoma
    University of Oklahoma)

  • Shelley S. Kane

    (University of Oklahoma
    University of Oklahoma)

  • Ekram Hossain

    (University of Oklahoma
    University of Oklahoma)

  • Jeroen Pollet

    (Baylor College of Medicine)

  • Maria Elena Bottazzi

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Peter J. Hotez

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Kathryn M. Jones

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Laura-Isobel McCall

    (University of Oklahoma
    University of Oklahoma
    University of Oklahoma
    San Diego State University)

Abstract

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, these results reveal molecular mechanisms of CD treatment based on simultaneous effects on the pathogen and on host small molecule responses, and expand our understanding of clinical treatment failure in CD. This link between infection and subsequent persistent small molecule perturbation broadens our understanding of infectious disease sequelae.

Suggested Citation

  • Zongyuan Liu & Rebecca Ulrich vonBargen & April L. Kendricks & Kate Wheeler & Ana Carolina Leão & Krithivasan Sankaranarayanan & Danya A. Dean & Shelley S. Kane & Ekram Hossain & Jeroen Pollet & Maria, 2023. "Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42247-w
    DOI: 10.1038/s41467-023-42247-w
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    References listed on IDEAS

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    1. Sophia Doll & Martina Dreßen & Philipp E. Geyer & Daniel N. Itzhak & Christian Braun & Stefanie A. Doppler & Florian Meier & Marcus-Andre Deutsch & Harald Lahm & Rüdiger Lange & Markus Krane & Matthia, 2017. "Region and cell-type resolved quantitative proteomic map of the human heart," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Lyda Z Rojas & Marija Glisic & Laura Pletsch-Borba & Luis E Echeverría & Wichor M Bramer & Arjola Bano & Najada Stringa & Asija Zaciragic & Bledar Kraja & Eralda Asllanaj & Rajiv Chowdhury & Carlos A , 2018. "Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 12(6), pages 1-20, June.
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