Persistent Biofluid Small-Molecule Alterations Induced by Trypanosoma cruzi Infection Are Not Restored by Parasite Elimination

Chagas disease (CD), caused by Trypanosoma cruzi (T. cruzi) protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome of T. cruzi-infected mice via liquid chromat...

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Bibliographic Details
Published in:ACS infectious diseases 2023-11, Vol.9 (11), p.2173-2189
Main Authors: Dean, Danya A., Roach, Jarrod, Ulrich vonBargen, Rebecca, Xiong, Yi, Kane, Shelley S., Klechka, London, Wheeler, Kate, Jimenez Sandoval, Michael, Lesani, Mahbobeh, Hossain, Ekram, Katemauswa, Mitchelle, Schaefer, Miranda, Harris, Morgan, Barron, Sayre, Liu, Zongyuan, Pan, Chongle, McCall, Laura-Isobel
Format: Article
Language:English
Subjects:
Animals
Chagas Disease - parasitology
Humans
Mice
Parasites
Trypanocidal Agents - pharmacology
Trypanocidal Agents - therapeutic use
Trypanosoma cruzi
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Summary:Chagas disease (CD), caused by Trypanosoma cruzi (T. cruzi) protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome of T. cruzi-infected mice via liquid chromatography tandem mass spectrometry of clinically accessible biofluids: saliva, urine, and plasma. Urine was the most indicative of infection status across mouse and parasite genotypes. Metabolites perturbed by infection in urine include kynurenate, acylcarnitines, and threonylcarbamoyladenosine. Based on these results, we sought to implement urine as a tool for the assessment of CD treatment success. Strikingly, it was found that mice with parasite clearance following benznidazole antiparasitic treatment had an overall urine metabolome comparable to that of mice that failed to clear parasites. These results provide a complementary hypothesis to explain clinical trial data in which benznidazole treatment did not improve patient outcomes in late-stage disease, even in patients with successful parasite clearance. Overall, this study provides insights into new small-molecule-based CD diagnostic methods and a new approach to assess functional responses to treatment.
ISSN:2373-8227
2373-8227
DOI:10.1021/acsinfecdis.3c00261