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Parasites & Vectors Dec 2016The evolutionary history and ecological associations of Trypanosoma cruzi, the need to identify genetic markers that can distinguish parasite subpopulations, and...
BACKGROUND
The evolutionary history and ecological associations of Trypanosoma cruzi, the need to identify genetic markers that can distinguish parasite subpopulations, and understanding the parasite's evolutionary and selective processes have been the subject of a significant number of publications since 1998, the year when the first DNA sequence analysis for the species was published.
METHODS
The current analysis systematizes and re-analyzes this original research, focusing on critical methodological and analytical variables and results that have given rise to interpretations of putative patterns of genetic diversity and diversification of T. cruzi lineages, discrete typing units (DTUs), and populations, and their associations with hosts, vectors, and geographical distribution that have been interpreted as evidence for parasite subpopulation specificities.
RESULTS
Few studies use hypothesis-driven or quantitative analysis for T. cruzi phylogeny (16/58 studies) or phylogeography (10/13). Among these, only one phylogenetic and five phylogeographic studies analyzed molecular markers directly from tissues (i.e. not from isolates). Analysis of T. cruzi DTU or lineage niche and its geographical projection demonstrate extensive sympatry among all clades across the continent and no significant niche differences among DTUs. DTU beta-diversity was high, indicating diverse host assemblages across regions, while host dissimilarity was principally due to host species turnover and to a much lesser degree to nestedness. DTU-host order specificities appear related to trophic or microenvironmental interactions.
CONCLUSIONS
More rigorous study designs and analyses will be required to discern evolutionary processes and the impact of landscape modification on population dynamics and risk for T. cruzi transmission to humans.
Topics: Animals; Chagas Disease; Genetic Variation; Genotype; Host Specificity; Humans; Phylogeny; Phylogeography; Trypanosoma cruzi
PubMed: 27923409
DOI: 10.1186/s13071-016-1918-2 -
Parasites & Vectors Jun 2022Reliable diagnostic tools are needed to choose the appropriate treatment and proper control measures for animal trypanosomoses, some of which are pathogenic. Trypanosoma... (Review)
Review
Reliable diagnostic tools are needed to choose the appropriate treatment and proper control measures for animal trypanosomoses, some of which are pathogenic. Trypanosoma cruzi, for example, is responsible for Chagas disease in Latin America. Similarly, pathogenic animal trypanosomoses of African origin (ATAO), including a variety of Trypanosoma species and subspecies, are currently found in Africa, Latin America and Asia. ATAO limit global livestock productivity and impact food security and the welfare of domestic animals. This review focusses on implementing previously reviewed diagnostic methods, in a complex epizootiological scenario, by critically assessing diagnostic results at the individual or herd level. In most cases, a single diagnostic method applied at a given time does not unequivocally identify the various parasitological and disease statuses of a host. These include "non-infected", "asymptomatic carrier", "sick infected", "cured/not cured" and/or "multi-infected". The diversity of hosts affected by these animal trypanosomoses and their vectors (or other routes of transmission) is such that integrative, diachronic approaches are needed that combine: (i) parasite detection, (ii) DNA, RNA or antigen detection and (iii) antibody detection, along with epizootiological information. The specificity of antibody detection tests is restricted to the genus or subgenus due to cross-reactivity with other Trypanosoma spp. and Trypanosomatidae, but sensitivity is high. The DNA-based methods implemented over the last three decades have yielded higher specificity and sensitivity for active infection detection in hosts and vectors. However, no single diagnostic method can detect all active infections and/or trypanosome species or subspecies. The proposed integrative approach will improve the prevention, surveillance and monitoring of animal trypanosomoses with the available diagnostic tools. However, further developments are required to address specific gaps in diagnostic methods and the sustainable control or elimination of these diseases.
Topics: Africa; Animals; Animals, Domestic; Chagas Disease; Trypanosoma; Trypanosoma cruzi; Trypanosomiasis
PubMed: 35761373
DOI: 10.1186/s13071-022-05352-1 -
Parasitology May 2023The aquatic and terrestrial clades of species of could provide insight into the evolutionary history of the genus, as well as complementary information for biomedical...
The aquatic and terrestrial clades of species of could provide insight into the evolutionary history of the genus, as well as complementary information for biomedical studies of medically and economically important species of . The ecological interactions and phylogeny of aquatic trypanosomes are currently not well-understood, mostly due to their complex life cycles and a deficiency of data. The species of from African anuran hosts are of the least understood taxa in the genus. Trypanosomes were collected from South African frogs and subjected to morphological and phylogenetic analyses. This study redescribes () Laveran, 1904 and () Pienaar, 1962, with morphological and molecular data. The present study aims to create a platform for further future research on African anuran trypanosomes.
Topics: Animals; Phylogeny; Trypanosoma; Anura
PubMed: 36883296
DOI: 10.1017/S0031182023000203 -
Trends in Parasitology Feb 2019Inheritance of the single mitochondrial nucleoid (kinetoplast) in the trypanosome requires numerous proteins, many of whose precise roles are unclear. By considering... (Review)
Review
Inheritance of the single mitochondrial nucleoid (kinetoplast) in the trypanosome requires numerous proteins, many of whose precise roles are unclear. By considering kinetoplast DNA (kDNA) as a template for cleavage into two equal-size networks, we predicted sets of mutant kinetoplasts associated with defects in each of the five steps in the kinetoplast cycle. Comparison of these kinetoplasts with those obtained after gene knockdowns enabled assignment of proteins to five classes - kDNA synthesis, site of scission selection, scission, separation, and partitioning. These studies highlight how analysis of mutant kinetoplast phenotypes may be used to predict functional categories of proteins involved in the biogenesis of kinetoplasts.
Topics: DNA, Kinetoplast; Mutation; Protozoan Proteins; Terminology as Topic; Trypanosoma
PubMed: 30638954
DOI: 10.1016/j.pt.2018.11.002 -
Genes Jun 2020Leishmaniasis ( species), sleeping sickness (), and Chagas disease () are devastating and globally spread diseases caused by trypanosomatid parasites. At present, drugs... (Review)
Review
Leishmaniasis ( species), sleeping sickness (), and Chagas disease () are devastating and globally spread diseases caused by trypanosomatid parasites. At present, drugs for treating trypanosomatid diseases are far from ideal due to host toxicity, elevated cost, limited access, and increasing rates of drug resistance. Technological advances in parasitology, chemistry, and genomics have unlocked new possibilities for novel drug concepts and compound screening technologies that were previously inaccessible. In this perspective, we discuss current models used in drug-discovery cascades targeting trypanosomatids (from in vitro to in vivo approaches), their use and limitations in a biological context, as well as different examples of recently discovered lead compounds.
Topics: Animals; Anthelmintics; Cheminformatics; Drug Discovery; Genome, Protozoan; Genomics; Humans; Trypanosoma; Trypanosomiasis
PubMed: 32610603
DOI: 10.3390/genes11070722 -
Genome Biology and Evolution Aug 2017Trypanosomes cause a variety of diseases in man and domestic animals in Africa, Latin America, and Asia. In the Trypanozoon subgenus, Trypanosoma brucei gambiense and...
Trypanosomes cause a variety of diseases in man and domestic animals in Africa, Latin America, and Asia. In the Trypanozoon subgenus, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense cause human African trypanosomiasis, whereas Trypanosoma brucei brucei, Trypanosoma evansi, and Trypanosoma equiperdum are responsible for nagana, surra, and dourine in domestic animals, respectively. The genetic relationships between T. evansi and T. equiperdum and other Trypanozoon species remain unclear because the majority of phylogenetic analyses has been based on only a few genes. In this study, we have conducted a phylogenetic analysis based on genome-wide SNP analysis comprising 56 genomes from the Trypanozoon subgenus. Our data reveal that T. equiperdum has emerged at least once in Eastern Africa and T. evansi at two independent occasions in Western Africa. The genomes within the T. equiperdum and T. evansi monophyletic clusters show extremely little variation, probably due to the clonal spread linked to the independence from tsetse flies for their transmission.
Topics: Africa, Eastern; Africa, Western; Genes, Protozoan; Genome, Protozoan; Genome-Wide Association Study; Phylogeny; Polymorphism, Single Nucleotide; Trypanosoma
PubMed: 28541535
DOI: 10.1093/gbe/evx102 -
Trends in Parasitology Mar 2020African trypanosomes are mainly transmitted by tsetse flies. In recent years there has been good progress in understanding how the parasites prepare for transmission,... (Review)
Review
African trypanosomes are mainly transmitted by tsetse flies. In recent years there has been good progress in understanding how the parasites prepare for transmission, detect their changed environment through the perception of different environmental cues, and respond by changing their developmental gene expression. In this review, we discuss the different signals and signaling mechanisms used by the parasites to carry out the early events necessary for their establishment in the fly. We also compare Trypanosoma brucei and Trypanosoma congolense, parasites that share a common pathway in the early stages of fly colonization but apparently use different mechanisms to achieve this.
Topics: Animals; Environment; Gene Expression Regulation, Developmental; Humans; Signal Transduction; Trypanosoma; Trypanosomiasis, African
PubMed: 32014419
DOI: 10.1016/j.pt.2019.12.011 -
RNA (New York, N.Y.) Feb 2004A number of mitochondrial proteins have been identified in Leishmania sp. and Trypanosoma brucei that may be involved in U-insertion/deletion RNA editing. Only a few of... (Review)
Review
A number of mitochondrial proteins have been identified in Leishmania sp. and Trypanosoma brucei that may be involved in U-insertion/deletion RNA editing. Only a few of these have yet been characterized sufficiently to be able to assign functional names for the proteins in both species, and most have been denoted by a variety of species-specific and laboratory-specific operational names, leading to a terminology confusion both within and outside of this field. In this review, we summarize the present status of our knowledge of the orthologous and unique putative editing proteins in both species and the functional motifs identified by sequence analysis and by experimentation. An online Supplemental sequence database (http://164.67.60.200/proteins/protsmini1.asp) is also provided as a research resource.
Topics: Amino Acid Motifs; Animals; Leishmania; Macromolecular Substances; Mitochondria; Mitochondrial Proteins; RNA Editing; Ribonuclease III; Trypanosoma
PubMed: 14730014
DOI: 10.1261/rna.5170704 -
PLoS Pathogens Jul 2021Animal African Trypanosomiasis (AAT) is a debilitating livestock disease prevalent across sub-Saharan Africa, a main cause of which is the protozoan parasite Trypanosoma...
Animal African Trypanosomiasis (AAT) is a debilitating livestock disease prevalent across sub-Saharan Africa, a main cause of which is the protozoan parasite Trypanosoma congolense. In comparison to the well-studied T. brucei, there is a major paucity of knowledge regarding the biology of T. congolense. Here, we use a combination of omics technologies and novel genetic tools to characterise core metabolism in T. congolense mammalian-infective bloodstream-form parasites, and test whether metabolic differences compared to T. brucei impact upon sensitivity to metabolic inhibition. Like the bloodstream stage of T. brucei, glycolysis plays a major part in T. congolense energy metabolism. However, the rate of glucose uptake is significantly lower in bloodstream stage T. congolense, with cells remaining viable when cultured in concentrations as low as 2 mM. Instead of pyruvate, the primary glycolytic endpoints are succinate, malate and acetate. Transcriptomics analysis showed higher levels of transcripts associated with the mitochondrial pyruvate dehydrogenase complex, acetate generation, and the glycosomal succinate shunt in T. congolense, compared to T. brucei. Stable-isotope labelling of glucose enabled the comparison of carbon usage between T. brucei and T. congolense, highlighting differences in nucleotide and saturated fatty acid metabolism. To validate the metabolic similarities and differences, both species were treated with metabolic inhibitors, confirming that electron transport chain activity is not essential in T. congolense. However, the parasite exhibits increased sensitivity to inhibition of mitochondrial pyruvate import, compared to T. brucei. Strikingly, T. congolense exhibited significant resistance to inhibitors of fatty acid synthesis, including a 780-fold higher EC50 for the lipase and fatty acid synthase inhibitor Orlistat, compared to T. brucei. These data highlight that bloodstream form T. congolense diverges from T. brucei in key areas of metabolism, with several features that are intermediate between bloodstream- and insect-stage T. brucei. These results have implications for drug development, mechanisms of drug resistance and host-pathogen interactions.
Topics: Animals; Lipid Regulating Agents; Mice; Trypanosoma brucei brucei; Trypanosoma congolense; Trypanosomiasis, African
PubMed: 34310651
DOI: 10.1371/journal.ppat.1009734 -
International Journal For Parasitology.... Dec 2021Kinetoplastid parasites are the causative agents of Chagas disease (CD), leishmaniasis and human African trypanosomiasis (HAT). Despite a sustained decrease in the...
Kinetoplastid parasites are the causative agents of Chagas disease (CD), leishmaniasis and human African trypanosomiasis (HAT). Despite a sustained decrease in the number of HAT cases, more efforts are needed to discover safe and effective therapies against CD and leishmaniasis. Kinetoplastid parasites lack the capability to biosynthesize purines de novo and thus critically depend on uptake and processing of purines from host cells. As such, modified purine nucleoside analogues may act as broad-spectrum antikinetoplastid agents. This study assessed the in vitro activity profile of 7-modified 6-methyl tubercidin derivatives against Trypanosoma cruzi, Leishmania infantum, Trypanosoma brucei brucei and T. b. rhodesiense, and led to the identification of analogues that display activity against all these species, such as 7-ethyl (13) and 7-chloro (7) analogues. These selected analogues also proved sufficiently stable in liver microsomes to warrant in vivo follow-up evaluation.
Topics: Antiprotozoal Agents; Humans; Nucleosides; Purines; Structure-Activity Relationship; Trypanosoma brucei brucei; Trypanosoma cruzi
PubMed: 34375904
DOI: 10.1016/j.ijpddr.2021.08.001