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The different stages of Trypanosoma cruzi. The image depicted the amastigote, epimastigote, and trypomastigote stages from T. cruzi and their membrane domains: nucleus (N); kinetoplast (K); flagellum (F); flagellar pocket (FP); and cell body (CB).
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Trypanosoma cruzi is the causal agent of Chagas’ disease which affects millions of people around the world mostly in Central and South America. T. cruzi expresses a wide variety of proteins on its surface membrane which has an important role in the biology of these parasites. Surface molecules of the parasites are the result of the environment to w...
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The parasite Trypanosoma cruzi is the causal agent of Chagas disease.It presents a wide biological and genetic diversity, therefore it is grouped into 6 taxonomic units..The strains Y, CL Brener and one strain isolated in Paraguaywere used in this study in order to determine their protein and antigenic profiles, applying techniques such as SDS-PAGE...
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... 14,15 However, the precise nature of this relationship remains incompletely understood. The surface of T. cruzi is rich in pathogen-associated molecular patterns, 16 while host tissue injury releases damage-associated molecular patterns. 17 Together, these molecular signatures serve as key triggers for activating the host's innate and adaptive immune responses. ...
Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human-and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.
... Over~1400 genes have been arranged in eight subfamilies, with special interest in the type I subfamily, which is associated with trans-sialidase/neuraminidase enzymatic activities [106]. Trans-sialidase has been localized in the cell body, flagellum, and flagellar pocket [107,108]. Endotrypanum, a lineage distantly related to Trypanosoma, has also shown high sialidase activity [109]. Herein, we confirmed an Endotrypanum-specific gene, which might be used in the sphingolipid pathway ( Figure 6 and Table S7). ...
The Leishmaniinae subfamily of the Trypanosomatidae contains both genus Zelonia (monoxenous) and Endotrypanum (dixenous). They are amongst the nearest known relatives of Leishmania, which comprises many human pathogens widespread in the developing world. These closely related lineages are models for the genomic biology of monoxenous and dixenous parasites. Herein, we used comparative genomics to identify the orthologous groups (OGs) shared among 26 Leishmaniinae species to investigate gene family expansion/contraction and applied two phylogenomic approaches to confirm relationships within the subfamily. The Endotrypanum monterogeii and Zelonia costaricensis genomes were assembled, with sizes of 29.9 Mb and 38.0 Mb and 9.711 and 12.201 predicted protein-coding genes, respectively. The genome of E. monterogeii displayed a higher number of multicopy cell surface protein families, including glycoprotein 63 and glycoprotein 46, compared to Leishmania spp. The genome of Z. costaricensis presents expansions of BT1 and amino acid transporters and proteins containing leucine-rich repeat domains, as well as a loss of ABC-type transporters. In total, 415 and 85 lineage-specific OGs were identified in Z. costaricensis and E. monterogeii. The evolutionary relationships within the subfamily were confirmed using the supermatrix (3384 protein-coding genes) and supertree methods. Overall, this study showed new expansions of multigene families in monoxenous and dixenous parasites of the subfamily Leishmaniinae.
... Trans sialidase (TS) superfamily has about 1430 gene members [98]. TS activity involves the transfer of sialic acid from host glycoconjugates to parasite mucins present in the plasma membrane of trypomastigotes. ...
... Cruzipain has been implicated in host-parasite interactions [117]. Some detailed characteristics of the T. cruzi surface molecules have been discussed elsewhere [98]. Taken together, T. cruzi employs many strategies to differentiate, survive, evade the immune system, and infect its host. ...
New anti-trypanosome drugs focusing on N-alpha terminal acetylation (Nt-acetylation) interference are necessary scientific inputs because currently, many of the drugs in use are unacceptably toxic; moreover, resistance is emerging. Nt-acetylation transfers an acetyl molecule to the N-alpha terminal of a protein by enzymes called N-alpha terminal acetyltransferases (Nats). Nats are grouped according to their amino acid sequence at the N-terminus where they acetylate. It is conserved in all kingdoms of life, and in humans, approximately 80% of proteins are thought to be Nt-acetylated. NatA-NatF and NatH identified in humans, and NatG has been observed in plants. Nats play critical roles in several cellular processes and integrity and have been suggested as possible drug targets to control different cancer diseases. NatA and NatC have been partially characterized in trypanosomes and shown to be essential for parasite viability. Biologically, the way parasites program their lives is embedded in their unique organelles, metabolic pathways, gene regulation, epigenetic gene activities, and many virulence factors including surface molecules. These characteristics and the different protein-coding genes involved could be Nt-acetylated, and the inhibition of Nats can deny the ability of trypanosomes to survive in any environment because many proteins can be simultaneously affected.
... The surface molecules of T. cruzi vary according to the evolutionary form but are mostly composed of mucin-type glycoproteins involved in protection and infectivity processes. Trans-sialidases, cruzipains, and others are also present in smaller amounts (for a complete review of the main molecules, see Pech-Canul et al. [39]). Comparative proteomic studies of different T. cruzi strains show significant differences in cell surface molecule composition, which appears to be closely related to the immunopathogenesis of the disease. ...
Chagas disease is one of the most important tropical infections in the world and mainly affects poor people. The causative agent is the hemoflagellate protozoan Trypanosoma cruzi, which circulates among insect vectors and mammals throughout the Americas. A large body of research on Chagas disease has shown the complexity of this zoonosis, and controlling it remains a challenge for public health systems. Although knowledge of Chagas disease has advanced greatly, there are still many gaps, and it is necessary to continue generating basic and applied research to create more effective control strategies. The aim of this review is to provide up-to-date information on the components of Chagas disease and highlight current trends in research. We hope that this review will be a starting point for beginners and facilitate the search for more specific information.
... Another similar example of antichagasic chatelicidin-related peptides is that of crotalicidin from the venom of C. durissus terrificus, which was able to inhibit all developmental forms of the T. cruzi benznidazole-resistant Y strain, showing high selectivity against trypomastigotes (SI > 200); as in the previous examples, crotalicidin induced necrosis in T. cruzi, causing several morphological alterations, including loss of membrane integrity and cell shrinkage [153]. The stage-selective antichagasic action displayed by snake venom components like BatxC or crotalicidin is likely related to stage-dependent changes on the parasite's membrane, including its surface protein composition [154]. ...
Malaria, leishmaniasis and Chagas disease are vector-borne protozoal infections with a disproportionately
high impact on the most fragile societies in the world, and despite malaria-focused research gained momentum in the past two decades, both trypanosomiases and leishmaniases remain neglected tropical diseases. Affordable effective drugs remain the mainstay of tackling this burden, but toxicicty, inneficiency against later stage disease, and drug resistance issues are serious shortcomings. One strategy to overcome these hurdles is to get new therapeutics or inspiration in nature. Indeed, snake venoms have been recognized as valuable sources of biomacromolecules, like peptides and proteins, with antiprotozoal activity. This review highlights major snake venom components active against at least one of the three aforementioned diseases, which include phospholipases A2, metalloproteases, L-amino acid oxidases, lectins, and oligopeptides. The relevance of this repertoire of biomacromolecules and the
bottlenecks in their clinical translation are discussed considering approaches that should increase the success rate in
this arduous task. Overall, this review underlines how venom-derived biomacromolecules could lead to pioneering antiprotozoal treatments and how the drug landscape for neglected diseases may be revolutionized by a closer look at venoms. Further investigations on poorly studied venoms is needed and could add new therapeutics to the pipeline.
... The second type is comprised by gene families encoded in multiple loci, displaying low sequence conservation such as mucins, trans-sialidases, TcGP63, amastin, TcTASV, mucin-associated surface proteins, and cruzipain. (49) The T. cruzi genome also presents non-coding repetitive sequences that participate in different cellular processes composing roughly half of the entire parasite genome. (44) Finally, thousands of transcriptionally active pseudogenes are also observed. ...
Chagas disease is an enduring public health issue in many Latin American countries, receiving insufficient investment in research and development. Strategies for disease control and management currently lack efficient pharmaceuticals, commercial diagnostic kits with improved sensitivity, and vaccines. Genetic heterogeneity of Trypanosoma cruzi is a key aspect for novel drug design since pharmacological technologies rely on the degree of conservation of parasite target proteins. Therefore, there is a need to expand the knowledge regarding parasite genetics which, if fulfilled, could leverage Chagas disease research and development, and improve disease control strategies. The growing capacity of whole-genome sequencing technology and its adoption as disease surveillance routine may be key for solving this long-lasting problem.
... Another similar example of antichagasic chatelicidin-related peptides is that of crotalicidin from the venom of C. durissus terrificus, which was able to inhibit all developmental forms of the T. cruzi benznidazole-resistant Y strain, showing high selectivity against trypomastigotes (SI > 200); as in the previous examples, crotalicidin induced necrosis in T. cruzi, causing several morphological alterations, including loss of membrane integrity and cell shrinkage [153]. The stage-selective antichagasic action displayed by snake venom components like BatxC or crotalicidin is likely related to stage-dependent changes on the parasite's membrane, including its surface protein composition [154]. ...
Malaria, leishmaniasis and Chagas disease are vector-borne protozoal infections with a disproportionately high impact on the most fragile societies in the world, and despite malaria-focused research gained momentum in the past two decades, both trypanosomiases and leishmaniases remain neglected tropical diseases. Affordable effective drugs remain the mainstay of tackling this burden, but toxicicty, inneficiency against later stage disease, and drug resistance issues are serious shortcomings. One strategy to overcome these hurdles is to get new therapeutics or inspiration in nature. Indeed, snake venoms have been recognized as valuable sources of bio-macromolecules, like peptides and proteins, with antiprotozoal activity. This review highlights major snake venom components active against at least one of the three aforementioned diseases, which include phospholi-pases A2, metalloproteases, L-amino acid oxidases, lectins, and oligopeptides. The relevance of this repertoire of biomacromolecules and the bottlenecks in their clinical translation are discussed considering approaches that should increase the success rate in this arduous task. Overall, this review underlines how venom-derived bio-macromolecules could lead to pioneering antiprotozoal treatments and how the drug landscape for neglected diseases may be revolutionized by a closer look at venoms. Further investigations on poorly studied venoms is needed and could add new therapeutics to the pipeline.
... Thus, parasite surface proteins have emerged as significant virulence factors [6] since the parasite surface coat remodeling is crucial to differentiation processes and infectivity, protecting from host defense mechanisms, in addition to cell attachment and infection [40,[45][46][47]. The trypanosome coat is mainly composed of glicophosphatidylinositol (GPI)anchored glycoconjugates of distinct nature, forming a layer of O-glycosylated mucins and glycoinosilphospholipidis (GIPLs). ...
Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. This protozoan developed several mechanisms to infect, propagate, and survive in different hosts. The specific expression of proteins is responsible for morphological and metabolic changes in different parasite stages along the parasite life cycle. The virulence strategies at the cellular and molecular levels consist of molecules responsible for mediating resistance mechanisms to oxidative damage, cellular invasion, and immune evasion, performed mainly by surface proteins. Since parasite surface coat remodeling is crucial to invasion and infectivity, surface proteins are essential virulence elements. Understanding the factors involved in these processes improves the knowledge of parasite pathogenesis. Genome sequencing has opened the door to high-throughput technologies, allowing us to obtain a deeper understanding of gene reprogramming along the parasite life cycle and identify critical molecules for survival. This review therefore focuses on proteins regulated during differentiation into infective forms considered virulence factors and addresses the current known mechanisms acting in the modulation of gene expression, emphasizing mRNA signals, regulatory factors, and protein complexes.
... La mitocondria tiene una apariencia ramificada y presenta una doble membrana directamente relacionada con el cinetoplasto, una estructura circular característica de los organismos del orden Kinetoplastida que contiene el DNA mitocondrial del parásito, conocido también como k-DNA. El cinetoplasto solo es circular en el estadio de tripomastigote, en amastigote y epimastigote es de forma alargada (Pech-Canul et al., 2017). El DNA mitocondrial asociado con el inicio del flagelo y cercano al núcleo, se organiza en estructuras atípicas llamadas maxicírculos y minicírculos, que representan cerca del 30% del genoma celular. ...
In 1909, Carlos Justiniano Chagas first described the clinical manifestations of Chagas disease. The hemoflagellate parasite Trypanosoma cruzi (agent) is characterized by the presence of a flagellum and of a cytostome, glycosomes, reservosomes, and a nucleus in its cytoplasm. The life cycle of T. cruzi begins when a vector defecates on the skin of a host; the feces contain metacyclic trypomastigotes, which infect vertebrate cells. The vectors of this disease are members of the subfamily Triatominae, nocturnal, hematophagous insects capable of locating hosts by heat detection. T. cruzi infection has effects on the biology of the triatomine insect, its behavior, gut function, immune system, and associated microbiota. In the mammalian host, the parasite activates innate immune responses, and host cytokines are key to either control the infection or progress to chronicity. T. cruzi exhibits a wide genetic diversity, and while it has been proved under laboratory conditions to show varying degrees if virulence and organ tropism, no clear association has been found between specific strains and the clinical picture of the disease. This review addresses the history of the discovery of Chagas disease and discusses recent aspects of T. cruzi biology that provide insight into the dynamics of transmission.
... La mitocondria tiene una apariencia ramificada y presenta una doble membrana directamente relacionada con el cinetoplasto, una estructura circular característica de los organismos del orden Kinetoplastida que contiene el DNA mitocondrial del parásito, conocido también como k-DNA. El cinetoplasto solo es circular en el estadio de tripomastigote, en amastigote y epimastigote es de forma alargada (Pech-Canul et al., 2017). El DNA mitocondrial asociado con el inicio del flagelo y cercano al núcleo, se organiza en estructuras atípicas llamadas maxicírculos y minicírculos, que representan cerca del 30% del genoma celular. ...
En 1909, Carlos Justiniano Chagas describió por primera vez las manifestaciones clínicas de la enfermedad de Chagas. El parásito hemoflagelado Trypanosoma cruzi (agente) se caracteriza por la presencia de un flagelo, y en su citoplasma presenta organelos como el citostoma, los glicosomas, los reservosomas y un núcleo. El ciclo de vida de T. cruzi se inicia cuando el vector defeca sobre la piel del hospedero sus heces contienen tripomastigotes metacíclicos, que infectan las células del vertebrado. Los vectores de esta enfermedad pertenecen a la Subfamilia Triatominae, insectos hematófagos, nocturnos y con la capacidad de localizar a sus hospederos mediante la detección del calor. T. cruzi tiene efectos en la biología del insecto triatomino, en su comportamiento, en el funcionamiento del intestino, su sistema inmunológico y la microbiota asociada. En el hospedero mamífero, el parásito activa la respuesta inmune innata, y las citocinas tienen un papel clave para controlar la infección o bien evolucionar a la cronicidad. T. cruzi presenta una amplia diversidad genética, y bajo condiciones de laboratorio se han demostrado sus diferentes grados de virulencia y tropismo hacia los órganos blanco; sin embargo, no existe una asociación clara entre las cepas y el comportamiento clínico de la enfermedad. Esta revisión aborda la historia del descubrimiento de la enfermedad de Chagas y discute aspectos recientes sobre la biología de T. cruzi para comprender la dinámica de su transmisión.
