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Anal Chem. 2017 Oct 3;89(19):10414-10421. doi: 10.1021/acs.analchem.7b02423. Epub 2017 Sep 22.

Mass Spectrometry-Based Chemical Cartography of a Cardiac Parasitic Infection.

Author information

1
Skaggs School of Pharmacy and Pharmaceutical Sciences, ‡Department of Computer Science, §Department of Pediatrics, ∥Center for Microbiome Innovation, and ⊥Collaborative Mass Spectrometry Innovation Center, University of California San Diego , La Jolla, California 92093, United States.

Abstract

Trypanosoma cruzi parasites are the causative agents of Chagas disease, a leading infectious form of heart failure whose pathogenesis is still not fully characterized. In this work, we applied untargeted liquid chromatography-tandem mass spectrometry to heart sections from T. cruzi-infected and uninfected mice. We combined molecular networking and three-dimensional modeling to generate chemical cartographical heart models. This approach revealed for the first time preferential parasite localization to the base of the heart and regiospecific distributions of nucleoside derivatives and eicosanoids, which we correlated to tissue-damaging immune responses. We further detected novel cardiac chemical signatures related to the severity and ultimate outcome of the infection. These signatures included differential representation of higher- vs lower-molecular-weight carnitine and phosphatidylcholine family members in specific cardiac regions of mice infected with lethal or nonlethal T. cruzi strains and doses. Overall, this work provides new insights into Chagas disease pathogenesis and presents an analytical chemistry approach that can be broadly applied to the study of host-microbe interactions.

PMID:
28892370
PMCID:
PMC6298790
DOI:
10.1021/acs.analchem.7b02423
[Indexed for MEDLINE]
Free PMC Article

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