Dataset Information

Comparative proteomic of Trypanosoma cruzi strains

ABSTRACT: Trypanosoma cruzi, the causative agent of Chagas disease, is a genetically diverse with TcI being the most widespread lineage in the Americas. The protein expression dynamics allows unravel the biological phenomena of pathogens such as disease development and evolution. A large number of studies have shown a direct relationship between genetic variability and the biological characteristics of T. cruzi. However, much remains to be explored regarding the impact of gene expression on the development and evolution of Chagas disease. Two-dimensional (2D) electrophoresis and mass-spectrometry were employed to characterize the global protein expression patterns of epimastigotes from four distinct TcI strains, which display different growth kinetics. Biological differences were identified and confirmed throug metabolic and morphometric assays. Statistical tests (parametric or non-parametric test, as appropriate for the experiment) were used to assess the significance of the observed differences. The Ascending hierarchical classification analysis shows two clusters, that were congruent with their growth kinetics. The proteins expressed in one or the other cluster were identified by mass spectrometry. These proteins were evaluated by independent biological assays, which showed that the parasite’s metabolic activity and morphology is significantly different between the two clusters. We conclude that the protein expression patterns displayed by epimastigotes from fast/slow growth TcI strains are correlated with various biological parameters, including intensity of metabolic activity, metabolic fuel usage and resistance to oxidative stress, as well as morphological characteristics, such as length of the flagellum.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Trypanosoma Cruzi

TISSUE(S): Cell Suspension Culture, Cell Culture

DISEASE(S): Chagas Disease

SUBMITTER: Functional Proteomics Platform FPP

LAB HEAD: Jaime Alfredo Costales Cordero

PROVIDER: PXD032748 | Pride | 2023-07-12

REPOSITORIES: Pride

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Publications

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

Telleria Jenny J Tibayrenc Michel M Del Salto Mendoza Michelle M Seveno Martial M Costales Jaime A JA

Experimental parasitology 20230708

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-dimensiona ...[more]

PMID: 37429537

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Project description:Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation. Certain tryptophan (Trp) metabolites have been identified as AhR ligands with regulatory functions. We investigated AhR expression, agonist response, ligand production, and AhR-dependent responses, such as IDO activation and regulatory T (Treg) cells induction, in two T.cruzi-infected mouse strains (B6 and Balb/c) showing different polymorphisms in AhR. Furthermore, we assessed the metabolic profile of Trp catabolites and AhR agonistic activity levels in plasma samples from patients with chronic Chagas disease (CCD) and healthy donors (HD) using a luciferase reporter assay and liquid chromatography-mass spectrophotometry (LC-MS) analysis. T. cruzi-infected B6 mice showed impaired AhR-dependent responses compared to Balb/c mice, including reduced IDO activity, kynurenine levels, Treg cell induction, CYP1A1 up-regulation, and AhR expression following agonist activation. Additionally, B6 mice exhibited no detectable 34 AhR agonist activity in plasma and displayed lower CYP1A1 up-regulation and AhR expression upon agonist activation. Similarly, CCC patients had decreased AhR agonistic activity in plasma compared to HD patients and exhibited dysregulation in Trp metabolic pathways, resulting in altered plasma metabolite profiles. Notably, patients with severe CCC specifically showed increased N-acetylserotonin levels in their plasma. The methods and findings presented here contribute to a better understanding of CCC development mechanisms and may identify potential specific biomarkers for T. cruzi infection and the severity of associated heart disease. These insights could be valuable in designing new therapeutic strategies. Ultimately, this research aims to establish the AhR agonistic activity and Trp metabolic profile in plasma as an innovative, non-invasive predictor of prognosis for chronic Chagas disease.

Dataset Information

Comparative proteomic of Trypanosoma cruzi strains

Publications

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

Similar Datasets

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