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Persistent Biofluid Small-Molecule Alterations Induced by Trypanosoma cruzi Infection Are Not Restored by Parasite
Danya A Dean1,2, Jarrod Roach1, Rebecca Ulrich vonBargen3
1Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
Insights
Researchers identified key urine metabolites for diagnosing Chagas disease (CD). Urine analysis revealed similar metabolic profiles in mice that cleared the parasite after treatment and those that did not, suggesting a new way to assess treatment effectiveness.
Area of Science:
- Parasitology
- Metabolomics
- Biochemistry
Background:
- Chagas disease (CD) presents diagnostic and treatment monitoring challenges.
- Current medical measures for diagnosing Trypanosoma cruzi (T. cruzi) infection and assessing treatment efficacy are insufficient.
Purpose of the Study:
- To identify reliable biomarkers for Chagas disease diagnosis and treatment monitoring.
- To investigate the utility of urine metabolomics for assessing T. cruzi infection and treatment response.
Main Methods:
- Analysis of urine, saliva, and plasma metabolomes in T. cruzi-infected mice using liquid chromatography tandem mass spectrometry.
- Comparison of metabolomic profiles between infected and uninfected mice, and between mice with and without parasite clearance post-treatment.
Main Results:
- Urine metabolome was the most indicative of infection status across different mouse and parasite genotypes.
- Key perturbed metabolites in infected mouse urine included kynurenate, acylcarnitines, and threonylcarbamoyladenosine.
- Urine metabolomes of mice achieving parasite clearance post-benznidazole treatment were comparable to those that failed to clear parasites.
Conclusions:
- Urine metabolomics offers a promising avenue for developing novel small-molecule-based diagnostic tools for Chagas disease.
- The study suggests a potential explanation for clinical observations where successful parasite clearance does not always correlate with improved patient outcomes in late-stage CD.
- Urine metabolite profiling may provide a new approach to assess functional responses to antiparasitic treatment in Chagas disease.
Abstract:
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.
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