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      Differential expression of proteins in genetically distinct Trypanosoma cruzi samples (TcI and TcII DTUs) isolated from chronic Chagas disease cardiac patients

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          Abstract

          Background

          Trypanosoma cruzi, a hemoflagellate protozoan parasite and the etiological agent of Chagas disease (CD), exhibits great genetic and biological diversity. Infected individuals may present clinical manifestations with different levels of severity. Several hypotheses have been proposed to attempt to correlate the diversity of clinical signs and symptoms to the genetic variability of T. cruzi. This work aimed to investigate the differential expression of proteins from two distinct genetic groups of T. cruzi (discrete typing units TcI and TcII), isolated from chronically infected individuals displaying the cardiac form of CD. For this purpose, epimastigote forms of the two isolates were cultured in vitro and the cells recovered for protein extraction. Comparative two-dimensional (2D) gel electrophoreses were performed and differentially expressed spots selected for identification by mass spectrometry, followed by database searching and protein categorization.

          Results

          The 2D electrophoretic profiles revealed the complex composition of the T. cruzi extracted proteome. Protein spots were distributed along the entire pH and molecular mass ranges attesting for the integrity of the protein preparations. In total, 46 differentially expressed proteins were identified present in 40 distinct spots found in the comparative gel analyses. Of these, 16 displayed upregulation in the gel from TcI-typed parasites and 24 appeared overexpressed in the gel from TcII-typed parasites. Functional characterization of differentially expressed proteins revealed major alterations associated with stress response, lipid and amino acid metabolism in parasites of the TcII isolate, whilst those proteins upregulated in the TcI sample were primarily linked to central metabolic pathways.

          Conclusions

          The comparative 2D-gel electrophoresis allowed detection of major differences in protein expression between two T. cruzi isolates, belonging to the TcI and TcII genotypes. Our findings suggest that patients displaying the cardiac form of the disease harbor parasites capable of exhibiting distinct proteomic profiles. This should be of relevance to disease prognosis and treatment.

          Electronic supplementary material

          The online version of this article (10.1186/s13071-018-3181-1) contains supplementary material, which is available to authorized users.

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          Most cited references50

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          The heat shock response: life on the verge of death.

          Organisms must survive a variety of stressful conditions, including sudden temperature increases that damage important cellular structures and interfere with essential functions. In response to heat stress, cells activate an ancient signaling pathway leading to the transient expression of heat shock or heat stress proteins (Hsps). Hsps exhibit sophisticated protection mechanisms, and the most conserved Hsps are molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. In this Review, we summarize the concepts of the protective Hsp network. Copyright © 2010 Elsevier Inc. All rights reserved.
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            The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications.

            The protozoan Trypanosoma cruzi, its mammalian reservoirs, and vectors have existed in nature for millions of years. The human infection, named Chagas disease, is a major public health problem for Latin America. T. cruzi is genetically highly diverse and the understanding of the population structure of this parasite is critical because of the links to transmission cycles and disease. At present, T. cruzi is partitioned into six discrete typing units (DTUs), TcI-TcVI. Here we focus on the current status of taxonomy-related areas such as population structure, phylogeographical and eco-epidemiological features, and the correlation of DTU with natural and experimental infection. We also summarize methods for DTU genotyping, available for widespread use in endemic areas. For the immediate future multilocus sequence typing is likely to be the gold standard for population studies. We conclude that greater advances in our knowledge on pathogenic and epidemiological features of these parasites are expected in the coming decade through the comparative analysis of the genomes from isolates of various DTUs. Copyright © 2012 Elsevier B.V. All rights reserved.
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              Trypanosoma cruzi genetic diversity: Something new for something known about Chagas disease manifestations, serodiagnosis and drug sensitivity.

              The genetic diversity of Trypanosoma cruzi, the protozoan agent of Chagas disease, is widely recognized. At present, T. cruzi is partitioned into seven discrete typing units (DTUs), TcI-TcVI and Tcbat. This article reviews the present knowledge on the parasite population structure, the evolutionary relationships among DTUs and their distinct, but not exclusive ecological and epidemiological associations. Different models for the origin of hybrid DTUs are examined, which agree that genetic exchange among T. cruzi populations is frequent and has contributed to the present parasite population structure. The geographic distribution of the prevalent DTUs in humans from the southern United States to Argentina is here presented and the circumstantial evidence of a possible association between T. cruzi genotype and Chagas disease manifestations is discussed. The available information suggests that parasite strains detected in patients, regardless of the clinical presentation, reflect the principal DTU circulating in the domestic transmission cycles of a particular region. In contrast, in several orally transmitted outbreaks, sylvatic strains are implicated. As a consequence of the genotypic and phenotypic differences of T. cruzi strains and the differential geographic distribution of DTUs in humans, regional variations in the sensitivity of the serological tests are verified. The natural resistance to benznidazole and nifurtimox, verified in vivo and in vitro for some parasite stocks, is not associated with any particular DTU, and does not explain the marked difference in the anti-parasitic efficacy of both drugs in the acute and chronic phases of Chagas disease. Throughout this review, it is emphasized that the interplay between parasite and host genetics should have an important role in the definition of Chagas disease pathogenesis, anti-T. cruzi immune response and chemotherapy outcome and should be considered in future investigations.
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                Author and article information

                Contributors
                maykontavares@yahoo.com.br
                karina.rubio@ufop.edu.br
                leandroxneves@gmail.com
                mjotoledo@uem.br
                wborges@ufop.edu.br
                delana@ufop.edu.br
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                29 November 2018
                29 November 2018
                2018
                : 11
                : 611
                Affiliations
                [1 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Programa de Pós-Graduação em Ciências Biológicas do Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Campus Universitário Morro do Cruzeiro, Universidade Federal de Ouro Preto, ; CEP, Ouro Preto, MG 35400-000 Brazil
                [2 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Departamento de Farmácia, Escola de Farmácia, Campus Universitário Morro do Cruzeiro, , Universidade Federal de Ouro Preto, ; CEP, Ouro Preto, MG 35400-000 Brazil
                [3 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Programa de Pós-Graduação em Biotecnologia do Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Campus Universitário Morro do Cruzeiro, Universidade Federal de Ouro Preto, ; CEP: 35400-000, Ouro Preto, MG Brazil
                [4 ]ISNI 0000 0001 2116 9989, GRID grid.271762.7, Departamento de Ciências Básicas da Saúde – Parasitologia, , Universidade Estadual de Maringá, ; CEP: 87020-900, Maringá, Paraná, PR Brazil
                [5 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Campus Universitário Morro do Cruzeiro, , Universidade Federal de Ouro Preto, ; CEP: 35400-000, Ouro Preto, MG Brazil
                [6 ]ISNI 0000 0004 0488 4317, GRID grid.411213.4, Departamento de Análises Clínicas, Escola de Farmácia, Campus Universitário Morro do Cruzeiro, , Universidade Federal de Ouro Preto, ; CEP: 35400-000, Ouro Preto, MG Brazil
                Article
                3181
                10.1186/s13071-018-3181-1
                6267078
                30497493
                d0c51a00-3919-45e9-8d70-37626267e200
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 July 2018
                : 31 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004901, Fundação de Amparo à Pesquisa do Estado de Minas Gerais;
                Award ID: APQ-00766-16
                Award ID: APQ-03367-16
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Parasitology
                trypanosoma cruzi,dtus,differential proteomics,chagas disease
                Parasitology
                trypanosoma cruzi, dtus, differential proteomics, chagas disease

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