Comparative proteomic analysis of trypomastigotes from Trypanosoma cruzi strains with different pathogenicity

Abstract

Chagas disease, caused by the parasite Trypanosoma cruzi, is one of the most neglected diseases in Latin America, being currently a global health problem. Its immunopathogenesis is still quite unknown. Moreover, there are important differences in pathogenicity between some different T. cruzi strains. For example, in mice, Y strain produces a high acute lethality while VFRA remains in the host mostly in a chronic manner.Comparative proteomic studies between T. cruzi strains represent a complement for transcriptomics and may allow the detection of relevant factors or distinctive functions. Here for the first time, we compared the proteome of trypomastigotes from 2 strains, Y and VFRA, analyzed by mass spectrometry. Gene ontology analysis were used to display similarities or differences in cellular components, biological processes and molecular functions. Also, we performed metabolic pathways enrichment analysis to detect the most relevant pathways in each strain.Although in general they have similar profiles in the different ontology groups, there were some particular interesting differences. Moreover, there were around 10% of different proteins between Y and VFRA strains, that were shared by other T. cruzi strains or protozoan species. They displayed many common enriched metabolic pathways but some others were uniquely enriched in one strain. Thus, we detected enriched antioxidant defenses in VFRA that could correlate with its ability to induce a chronic infection in mice controlling ROS production, while the Y strain revealed a great enrichment of pathways related with nucleotides and protein production, that could fit with its high parasite replication and lethality. In summary, Y and VFRA strains displayed comparable proteomes with some particular distinctions that could contribute to understand their different biological behaviors.

Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications

“…(3) Non-coding sequences and repetitive sequences, such as tandem repeats, retrotransposable elements and short repeat elements, which represent more than half of the genome affecting the methods of short-read sequencing above all as we explained before. Interestingly, around 50% of the genetic content of T. cruzi has unknown functions [47], which correlates with proteome studies of CL Brener, Dm28c, Y, and VFRA strains [69][70][71][72] in which around 40-50% of total proteins were of unknown function. This indicates how much we do not know yet about T. cruzi biology.…”

Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

“…This highlights the importance of the background of the host in the outcome of the infection [2,34]. Interestingly, by proteomic analysis, we have reported enriched antioxidant defenses in trypomastigotes of VFRA compared to Y strain [35], that could support the hypothesis that ROS production is detrimental for VFRA and for this reason VFRA would tend to increase these metabolic pathways to cope with the great generation of ROS by NOX2 among other enzymes.…”

The Complete Mitochondrial DNA of Trypanosoma cruzi: Maxicircles and Minicircles

“…Some are acute lethal strains as Y, whereas others, such as VFRA can produce a chronic infection in BALB/c mice ( Rodriguez et al., 2014 ). Furthermore, proteomic analysis, comparing strains with different pathogenicity, indicates that strains inducing chronic infection have enriched antioxidant defenses, while those inducing acute infections produce nucleotides and proteins involved in parasite replication and lethality ( Herreros-Cabello et al., 2019 ).…”

“…Concretely, the CSB-3 or UMS is the specific binding site of the UMS binding protein (UMSBP), which has been related with the minicircle replication and kDNA segregation ( Milman et al., 2007 ). UMSBP has been widely studied in Crithidia fasciculate ( Tzfati et al., 1995 ; Abu-Elneel et al., 1999 ; Abu-Elneel et al., 2001 ; Onn et al., 2006 ), but its presence has been revealed in other Trypanosomatids such as T. cruzi ( Milman et al., 2007 ; Herreros-Cabello et al., 2019 ), Leishmania donovani ( Singh et al., 2016 ) or T. brucei ( Milman et al., 2007 ). According to these studies the consensus sequence for each CSB, including T. cruzi , would be: CSB-1=AGGGGCGTTC, CSB-2=CCCCGTAC and CSB-3=GGGGTTGGTGTA.…”