2. Academic Validation
  3. Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease

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

  • Nat Commun. 2023 Oct 25;14(1):6769. doi: 10.1038/s41467-023-42247-w.
Zongyuan Liu 1 2,  Rebecca Ulrich vonBargen 2 3,  April L Kendricks 4,  Kate Wheeler 5,  Ana Carolina Leão 6,  Krithivasan Sankaranarayanan 2 7,  Danya A Dean 1 2,  Shelley S Kane 1 2,  Ekram Hossain 1 2,  Jeroen Pollet 6,  Maria Elena Bottazzi 6 8,  Peter J Hotez 6 8,  Kathryn M Jones 9 10,  Laura-Isobel McCall 11 12 13 14
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA.
  • 2 Laboratories of Molecular Anthropology and Microbiome Research, University of Oklahoma, Norman, OK, USA.
  • 3 Department of Biomedical Engineering, University of Oklahoma, Norman, OK, USA.
  • 4 Southern Star Medical Research Institute, Houston, TX, USA.
  • 5 Department of Biology, University of Oklahoma, Norman, OK, USA.
  • 6 Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
  • 7 Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK, USA.
  • 8 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  • 9 Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. kathrynj@bcm.edu.
  • 10 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. kathrynj@bcm.edu.
  • 11 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA. Lmccall@sdsu.edu.
  • 12 Laboratories of Molecular Anthropology and Microbiome Research, University of Oklahoma, Norman, OK, USA. Lmccall@sdsu.edu.
  • 13 Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK, USA. Lmccall@sdsu.edu.
  • 14 Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA. Lmccall@sdsu.edu.
PMID: 37880260 DOI: 10.1038/s41467-023-42247-w
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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