Comparative proteomic analysis of Trypanosoma cruzi TcI lineage epimastigotes unveils metabolic and phenotypic differences between fast- and slow-dividing strains

Trypanosoma cruzi, the causative agent of Chagas disease, is a genetically and phenotypically diverse species, divided into 5 main phylogenetic lineages (TcI to TcVI). TcI is the most widespread lineage in the Americas. Proteomics is a suitable tool to study the global protein expression dynamics in pathogens. Previous proteomic studies have revealed a link between (i) the genetic variability; (ii) the protein expression; and (iii) the biological characteristics of T. cruzi. Here, two-dimensional electrophoresis (2DE) and mass spectrometry were used to characterize the overall protein expression profiles of epimastigotes from four distinct TcI strains displaying different growth kinetics. Ascending hierarchical clustering analysis based on the global 2DE protein expression profiles grouped the strains under study into two clusters that were congruent with their fast or slow growth kinetics. A subset of proteins differentially expressed by the strains in each group were identified by mass spectrometry. Biological differences between the two groups, including use of glucose as an energy source, flagellum length, and metabolic activity, were predicted by proteomic analysis and confirmed by metabolic tests and microscopic measurements performed on the epimastigotes of each strain. Our results show that protein expression profiles are correlated with parasite phenotypes, which may in turn influence the parasite's virulence and transmission capacity.