Localized Cardiac Small Molecule Trajectories and Persistent Chemical Sequelae in Experimental Chagas Disease

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Oct 25

PMID 37880260

Authors

Zongyuan Liu

Rebecca Ulrich vonBargen

April L Kendricks

Kate Wheeler

Ana Carolina Leao

Krithivasan Sankaranarayanan

Danya A Dean

Shelley S Kane

Ekram Hossain

Jeroen Pollet

Maria Elena Bottazzi

Peter J Hotez

Kathryn M Jones

Laura-Isobel McCall

Affiliations

Soon will be listed here.

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.

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