Trypanosoma cruzi pathogenicity involves virulence factor expression and upregulation of bioenergetic and biosynthetic pathways

The molecular repertoire of Trypanosoma cruzi effects its virulence and impacts the clinical course of the resulting Chagas disease. This study aimed to determine the mechanism underlying the pathogenicity of T. cruzi. Two T. cruzi cell lines (C8C3 hvir and C8C3 lvir ), obtained from the clone H510 C8C3 and exhibiting different virulence phenotypes, were used to evaluate the parasite's infectivity in mice. The organ parasite load was analysed by qPCR. The proteomes of both T. cruzi cell lines were compared using nLC-MS/MS. Cruzipain (Czp), complement regulatory protein (CRP), trans-sialidase (TS), Tc-85, and sialylated epitope expression levels were evaluated by immunoblotting. High-virulence C8C3 hvir was highly infectious in mice and demonstrated three to five times higher infectivity in mouse myocardial cells than low-virulence C8C3 lvir . qPCR revealed higher parasite loads in organs of acute as well as chronically C8C3 hvir -infected mice than in those of C8C3 lvir -infected mice. Comparative quantitative proteomics revealed that 390 of 1547 identified proteins were differentially regulated in C8C3 hvir with respect to C8C3 lvir . Amongst these, 174 proteins were upregulated in C8C3 hvir and 216 were downregulated in C8C3 lvir . The upregulated proteins in C8C3 hvir were associated with the tricarboxylic acid cycle, ribosomal proteins, and redoxins. Higher levels of Czp, CRP, TS, Tc-85, and sialylated epitopes were expressed in C8C3 hvir than in C8C3 lvir . Thus, T. cruzi virulence may be related to virulence factor expression as well as upregulation of bioenergetic and biosynthetic pathways proteins.

Automated summary

The study aimed to determine the mechanism underlying the pathogenicity of T. cruzi. The results showed that high-virulence C8C3 hvir was highly infectious in mice and demonstrated higher parasite loads compared to low-virulence C8C3 lvir. Comparative proteomics revealed differential regulation of proteins associated with bioenergetic and biosynthetic pathways in C8C3 hvir. Furthermore, C8C3 hvir expressed higher levels of virulence factors such as Cruzipain, complement regulatory protein, trans-sialidase, Tc-85, and sialylated epitopes.