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Genes Oct 2020Chagas disease caused by the parasite affects millions of people. Although its first genome dates from 2005, its complexity hindered a complete assembly and annotation.... (Review)
Review
Chagas disease caused by the parasite affects millions of people. Although its first genome dates from 2005, its complexity hindered a complete assembly and annotation. However, the new sequencing methods have improved genome annotation of some strains elucidating the broad genetic diversity and complexity of this parasite. Here, we reviewed the genomic structure and regulation, the genetic diversity, and the analysis of the principal multi-gene families of the recent genomes for several strains. The telomeric and sub-telomeric regions are sites with high recombination events, the genome displays two different compartments, the core and the disruptive, and the genome plasticity seems to play a key role in the survival and the infection process. () genome is composed mainly of multi-gene families as the trans-sialidases, mucins, and mucin-associated surface proteins. Trans-sialidases are the most abundant genes in the genome and show an important role in the effectiveness of the infection and the parasite survival. Mucins and MASPs are also important glycosylated proteins of the surface of the parasite that play a major biological role in both insect and mammal-dwelling stages. Altogether, these studies confirm the complexity of genome revealing relevant concepts to better understand Chagas disease.
Topics: Animals; Chagas Disease; Gene Expression Regulation; Genome, Protozoan; Humans; Multigene Family; Protozoan Proteins; Transcription, Genetic; Trypanosoma cruzi
PubMed: 33066599
DOI: 10.3390/genes11101196 -
Acta Tropica Dec 2019Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute... (Review)
Review
Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute infection and chronic disease. Studies in experimental models have suggested that the protective immunity against T. cruzi infection requires the elicitation of Th1 cytokines, lytic antibodies and the concerted activities of macrophages, T helper cells, and cytotoxic T lymphocytes (CTLs). In this review, we summarize the research efforts in vaccine development to date and the challenges faced in achieving an efficient prophylactic or therapeutic vaccine against human CD.
Topics: Animals; Chagas Disease; Humans; Protozoan Vaccines; Trypanosoma cruzi
PubMed: 31513763
DOI: 10.1016/j.actatropica.2019.105168 -
Pathogens and Disease Dec 2015Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine... (Review)
Review
Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies.
Topics: Adaptive Immunity; Animals; Chagas Disease; Host-Pathogen Interactions; Humans; Immune Evasion; Immune Tolerance; Immunity, Innate; Trypanosoma cruzi
PubMed: 26438729
DOI: 10.1093/femspd/ftv082 -
Clinical Microbiology Reviews Oct 2011Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The... (Review)
Review
Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor-derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century.
Topics: Animals; Chagas Disease; Disease Transmission, Infectious; Endemic Diseases; Humans; Trypanosoma cruzi; United States
PubMed: 21976603
DOI: 10.1128/CMR.00005-11 -
PLoS Neglected Tropical Diseases Aug 2021We sequenced maxicircles from T. cruzi strains representative of the species evolutionary diversity by using long-read sequencing, which allowed us to uncollapse their...
We sequenced maxicircles from T. cruzi strains representative of the species evolutionary diversity by using long-read sequencing, which allowed us to uncollapse their repetitive regions, finding that their real lengths range from 35 to 50 kb. T. cruzi maxicircles have a common architecture composed of four regions: coding region (CR), AT-rich region, short (SR) and long repeats (LR). Distribution of genes, both in order and in strand orientation are conserved, being the main differences the presence of deletions affecting genes coding for NADH dehydrogenase subunits, reinforcing biochemical findings that indicate that complex I is not functional in T. cruzi. Moreover, the presence of complete minicircles into maxicircles of some strains lead us to think about the origin of minicircles. Finally, a careful phylogenetic analysis was conducted using coding regions of maxicircles from up to 29 strains, and 1108 single copy nuclear genes from all of the DTUs, clearly establishing that taxonomically T. cruzi is a complex of species composed by group 1 that contains clades A (TcI), B (TcIII) and D (TcIV), and group 2 (1 and 2 do not coincide with groups I and II described decades ago) containing clade C (TcII), being all hybrid strains of the BC type. Three variants of maxicircles exist in T. cruzi: a, b and c, in correspondence with clades A, B, and C from mitochondrial phylogenies. While A and C carry maxicircles a and c respectively, both clades B and D carry b maxicircle variant; hybrid strains also carry the b- variant. We then propose a new nomenclature that is self-descriptive and makes use of both the phylogenetic relationships and the maxicircle variants present in T. cruzi.
Topics: Chagas Disease; Evolution, Molecular; Genetic Variation; Genome, Protozoan; Humans; NADH Dehydrogenase; Phylogeny; Protozoan Proteins; Trypanosoma cruzi
PubMed: 34437557
DOI: 10.1371/journal.pntd.0009719 -
Memorias Do Instituto Oswaldo Cruz May 2015Several different models of Trypanosoma cruzi evolution have been proposed. These models suggest that scarce events of genetic exchange occurred during the evolutionary... (Review)
Review
Several different models of Trypanosoma cruzi evolution have been proposed. These models suggest that scarce events of genetic exchange occurred during the evolutionary history of this parasite. In addition, the debate has focused on the existence of one or two hybridisation events during the evolution of T. cruzi lineages. Here, we reviewed the literature and analysed available sequence data to clarify the phylogenetic relationships among these different lineages. We observed that TcI, TcIII and TcIV form a monophyletic group and that TcIII and TcIV are not, as previously suggested, TcI-TcII hybrids. Particularly, TcI and TcIII are sister groups that diverged around the same time that a widely distributed TcIV split into two clades (TcIVS and TcIVN). In addition, we collected evidence that TcIII received TcIVS kDNA by introgression on several occasions. Different demographic hypotheses (surfing and asymmetrical introgression) may explain the origin and expansion of the TcIII group. Considering these hypotheses, genetic exchange should have been relatively frequent between TcIII and TcIVS in the geographic area in which their distributions overlapped. In addition, our results support the hypothesis that two independent hybridisation events gave rise to TcV and TcVI. Consequently, TcIVS kDNA was first transferred to TcIII and later to TcV and TcVI in TcII/TcIII hybridisation events.
Topics: Biological Evolution; DNA, Protozoan; Genetic Variation; Genotype; Hybridization, Genetic; Mitochondria; Phylogeny; Sequence Analysis, DNA; Trypanosoma cruzi
PubMed: 25807469
DOI: 10.1590/0074-02760140401 -
Molecular Microbiology May 2021Trypanosoma cruzi is a unicellular parasite and the etiologic agent of Chagas disease. The parasite has a digenetic life cycle alternating between mammalian and insect... (Review)
Review
Trypanosoma cruzi is a unicellular parasite and the etiologic agent of Chagas disease. The parasite has a digenetic life cycle alternating between mammalian and insect hosts, where it faces a variety of environmental conditions to which it must adapt in order to survive. The adaptation to these changes is mediated by signaling pathways that coordinate the cellular responses to the new environmental settings. Major environmental changes include temperature, nutrient availability, ionic composition, pH, osmolarity, oxidative stress, contact with host cells and tissues, host immune response, and intracellular life. Some of the signaling pathways and second messengers potentially involved in the response to these changes have been elucidated in recent years and will be the subject of this review.
Topics: Adaptation, Biological; Animals; Chagas Disease; Humans; Oxidative Stress; Signal Transduction; Trypanosoma cruzi
PubMed: 33034088
DOI: 10.1111/mmi.14621 -
Parasites & Vectors Feb 2018Trypanosoma cruzi uses several strategies to survive in different hosts. A key step in the life-cycle of this parasite is metacyclogenesis, which involves various...
BACKGROUND
Trypanosoma cruzi uses several strategies to survive in different hosts. A key step in the life-cycle of this parasite is metacyclogenesis, which involves various morphological, biochemical, and genetic changes that induce the differentiation of non-pathogenic epimastigotes into pathogenic metacyclic trypomastigotes. During metacyclogenesis, T. cruzi displays distinct morphologies and ultrastructural features, which have not been fully characterized.
RESULTS
We performed a temporal description of metacyclogenesis using different microscopy techniques that resulted in the identification of three intermediate forms of T. cruzi: intermediates I, II and III. Such classification was based on morphological and ultrastructural aspects as the location of the kinetoplast in relation to the nucleus, kinetoplast shape and kDNA topology. Furthermore, we suggested that metacyclic trypomastigotes derived from intermediate forms that had already detached from the substrate. We also found that changes in the kinetoplast morphology and kDNA arrangement occurred only after the repositioning of this structure toward the posterior region of the cell body. These changes occurred during the later stages of differentiation. In contrast, changes in the nucleus shape began as soon as metacyclogenesis was initiated, while changes in nuclear ultrastructure, such as the loss of the nucleolus, were only observed during later stages of differentiation. Finally, we found that kDNA networks of distinct T. cruzi forms present different patterns of DNA topology.
CONCLUSIONS
Our study of T. cruzi metacyclogenesis revealed important aspects of the morphology and ultrastructure of this intriguing cell differentiation process. This research expands our understanding of this parasite's fascinating life-cycle. It also highlights the study of T. cruzi as an important and exciting model system for investigating diverse aspects of cellular, molecular, and evolutionary biology.
Topics: Cell Differentiation; Microscopy; Organelles; Trypanosoma cruzi
PubMed: 29409544
DOI: 10.1186/s13071-018-2664-4 -
Genomics Jan 2020Trypanosoma cruzi is the etiologic agent of Chagas disease, a life-threatening disease that affects different tissues. Within its mammalian host, T. cruzi develops... (Review)
Review
Trypanosoma cruzi is the etiologic agent of Chagas disease, a life-threatening disease that affects different tissues. Within its mammalian host, T. cruzi develops molecular strategies for successful invasion of different cell types and adaptation to the intracellular environment. Conversely, the host cell responds to the infection by activating intracellular pathways to control parasite replication. Here, we reviewed genome-wide expression studies based on microarray and RNA-seq data from both parasite and host genes generated from animal models of infection as well as from Chagas disease patients. As expected, analyses of T. cruzi genes highlighted changes related to parasite energy metabolism and cell surface molecules, whereas host cell transcriptome emphasized the role of immune response genes. Besides allowing a better understanding of mechanisms behind the pathogenesis of Chagas disease, these studies provide essential information for the development of new therapies as well as biomarkers for diagnosis and assessment of disease progression.
Topics: Animals; Chagas Cardiomyopathy; Chagas Disease; Fibroblasts; Humans; Life Cycle Stages; Mice; RNA, Untranslated; Transcriptome; Trypanosoma cruzi
PubMed: 31229555
DOI: 10.1016/j.ygeno.2019.06.015 -
Frontiers in Cellular and Infection... 2020The regulation of gene expression in trypanosomatids occurs mainly at the post-transcriptional level. In the case of , the characterization of messenger...
The regulation of gene expression in trypanosomatids occurs mainly at the post-transcriptional level. In the case of , the characterization of messenger ribonucleoprotein (mRNP) particles has allowed the identification of several classes of RNA binding proteins (RBPs), as well as non-canonical RBPs, associated with mRNA molecules. The protein composition of the mRNPs as well as the localization and functionality of the mRNAs depend on their associated proteins. mRNPs can also be organized into larger complexes forming RNA granules, which function as stress granules or P-bodies depending on the associated proteins. The fate of mRNAs in the cell, and consequently the genes expressed, depends on the set of proteins associated with the messenger molecule. These proteins allow the coordinated expression of mRNAs encoding proteins that are related in function, resulting in the formation of post-transcriptional operons. However, the puzzle posed by the combinatorial association of sets of RBPs with mRNAs and how this relates to the expressed genes remain to be elucidated. One important tool in this endeavor is the use of the CRISPR/CAS system to delete genes encoding RBPs, allowing the evaluation of their effect on the formation of mRNP complexes and associated mRNAs in the different compartments of the translation machinery. Accordingly, we recently established this methodology for and deleted the genes encoding RBPs containing zinc finger domains. In this manuscript, we will discuss the data obtained and the potential of the CRISPR/CAS methodology to unveil the role of RBPs in gene expression regulation.
Topics: Gene Expression Regulation; Protozoan Proteins; RNA, Messenger; RNA-Binding Proteins; Trypanosoma cruzi
PubMed: 32154189
DOI: 10.3389/fcimb.2020.00056