Abstract
The etiological agent of Chagas disease, Trypanosoma cruzi, is a complex of seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution requires understanding the parasite origin and population structure. In this study, we introduce the PhyloQuant approach to infer the evolutionary relationships between organisms based on differential mass spectrometry-based quantitative features. In particular, large scale quantitative bottom-up proteomics features (MS1, iBAQ and LFQ) were analyzed using maximum parsimony, showing a correlation between T. cruzi DTUs and closely related trypanosomes’ protein expression and sequence-based clustering. Character mapping enabled the identification of synapomorphies, herein the proteins and their respective expression profiles that differentiate T. cruzi DTUs and trypanosome species. The distance matrices based on phylogenetics and PhyloQuant clustering showed statistically significant correlation highlighting the complementarity between the two strategies. Moreover, PhyloQuant allows the identification of differentially regulated and strain/DTU/species-specific proteins, and has potential application in the identification of specific biomarkers and candidate therapeutic targets.
Highlights
The etiological agent of Chagas disease, Trypanosoma cruzi, is a complex of seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat
In this study, an approach to typing and evolutionary inference between organisms based on systems-wide protein expression profiles is described, and was applied to trypanosomes of the subgenus Schizotrypanum, a monophyletic assemblage nested in the clade T. cruzi comprising mostly trypanosomes of bats, and two species infective to mammals in general, including humans: the pathogenic T. cruzi and the non-pathogenic T. rangeli[34,35,59,60,61,62]
This approach is based on different biomolecular features obtained by bottom-up large scale mass spectrometry-based quantitative proteomics analysis (MS1, intensity-based absolute quantification (iBAQ) and labelfree quantification (LFQ)) followed by maximum parsimony (MP), an evolutionary criterion to infer evolutionary distances between strains/species
Summary
The etiological agent of Chagas disease, Trypanosoma cruzi, is a complex of seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution requires understanding the parasite origin and population structure. Trypanosoma cruzi is a protistan parasite agent of Chagas disease (American trypanosomiasis), a zoonotic disease endemic in 21 Latin American countries[1] with ~25 million people at risk of infection. The parasite’s DTU has been implicated as one relevant factor influencing clinical variations of the disease[24,27,36], drug resistance/susceptibility[37,38], pathogenicity in mice[38], and vector competence[18,39]. Other factors influencing disease outcome include mixed infections, infection routes, host genetics and a range of eco-geographical factors[32,40,41]
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