Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease
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 tra...
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Published in | Nature communications Vol. 14; no. 1; p. 6769 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
25.10.2023
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
The impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by
Trypanosoma cruzi
infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-023-42247-w |