Spatial metabolomics identifies localized chemical changes in heart tissue during chronic cardiac Chagas Disease

Area of Science:

• Infectious Diseases
• Parasitology
• Metabolomics

Background:

• Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease with significant cardiac complications.
• Chronic CD pathogenesis and cardiac manifestations remain incompletely understood.
• Current understanding lacks insight into the localized metabolic impact of infection within the heart.

Purpose of the Study:

• To investigate the localized impact of chronic Chagas disease on the cardiac metabolome.
• To compare the effects of two divergent Trypanosoma cruzi strains on host cardiac metabolism.
• To identify specific metabolic pathways and chemical families altered by chronic infection.

Main Methods:

• Spatial metabolomics (chemical cartography) applied to cardiac tissue from infected and uninfected mice.
• Analysis of localized chemical differences in cardiac regions.
• Identification of discriminatory chemical families, including acylcarnitines and glycerophosphocholines.

Main Results:

• Chronic Trypanosoma cruzi infection induces distinct chemical differences in localized cardiac regions.
• These metabolically altered sites were spatially distinct from areas of highest parasite burden.
• Acylcarnitines and glycerophosphocholines were identified as key discriminatory chemical families.

Conclusions:

• Spatial metabolomics reveals global and positional metabolic alterations in the heart during chronic Chagas disease, common across different parasite strains.
• The study highlights infection-modulated pathways and provides insights into Chagas disease pathogenesis.
• A systematic spatial approach is advantageous for understanding infectious disease tropism and host-pathogen interactions.