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Parasites & Vectors May 2019Equine trypanosomosis is a complex of infectious diseases called dourine, nagana and surra. It is caused by several species of the genus Trypanosoma that are transmitted... (Review)
Review
Equine trypanosomosis is a complex of infectious diseases called dourine, nagana and surra. It is caused by several species of the genus Trypanosoma that are transmitted cyclically by tsetse flies, mechanically by other haematophagous flies, or sexually. Trypanosoma congolense (subgenus Nannomonas) and T. vivax (subgenus Dutonella) are genetically and morphologically distinct from T. brucei, T. equiperdum and T. evansi (subgenus Trypanozoon). It remains controversial whether the three latter taxa should be considered distinct species. Recent outbreaks of surra and dourine in Europe illustrate the risk and consequences of importation of equine trypanosomosis with infected animals into non-endemic countries. Knowledge on the epidemiological situation is fragmentary since many endemic countries do not report the diseases to the World Organisation for Animal Health, OIE. Other major obstacles to the control of equine trypanosomosis are the lack of vaccines, the inability of drugs to cure the neurological stage of the disease, the inconsistent case definition and the limitations of current diagnostics. Especially in view of the ever-increasing movement of horses around the globe, there is not only the obvious need for reliable curative and prophylactic drugs but also for accurate diagnostic tests and algorithms. Unfortunately, clinical signs are not pathognomonic, parasitological tests are not sufficiently sensitive, serological tests miss sensitivity or specificity, and molecular tests cannot distinguish the taxa within the Trypanozoon subgenus. To address the limitations of the current diagnostics for equine trypanosomosis, we recommend studies into improved molecular and serological tests with the highest possible sensitivity and specificity. We realise that this is an ambitious goal, but it is dictated by needs at the point of care. However, depending on available treatment options, it may not always be necessary to identify which trypanosome taxon is responsible for a given infection.
Topics: Animals; Dourine; Enzyme-Linked Immunosorbent Assay; Horse Diseases; Horses; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Sensitivity and Specificity; Serologic Tests; Trypanosoma; Trypanosoma brucei brucei; Trypanosoma congolense; Trypanosoma vivax; Trypanosomiasis
PubMed: 31092285
DOI: 10.1186/s13071-019-3484-x -
Microbiology (Reading, England) Aug 2023Years of research have shown us that unicellular organisms do not exist entirely in isolation, but rather that they are capable of an altogether far more sociable way of... (Review)
Review
Years of research have shown us that unicellular organisms do not exist entirely in isolation, but rather that they are capable of an altogether far more sociable way of living. Single cells produce, receive and interpret signals, coordinating and changing their behaviour according to the information received. Although this cell-cell communication has long been considered the norm in the bacterial world, an increasing body of knowledge is demonstrating that single-celled eukaryotic parasites also maintain active social lives. This communication can drive parasite development, facilitate the invasion of new niches and, ultimately, influence infection outcome. In this review, I present the evidence for cell-cell communication during the life cycle of the African trypanosomes, from their mammalian hosts to their insect vectors, and reflect on the many remaining unanswered questions in this fascinating field.
Topics: Animals; Trypanosoma; Cell Communication; Eukaryota; Insect Vectors; Mammals
PubMed: 37643128
DOI: 10.1099/mic.0.001388 -
Biochimica Et Biophysica Acta.... Apr 2021Trypanosoma cruzi, and the T. brucei group of parasites cause neglected diseases that affect millions of people around the world. These unicellular microorganisms have... (Review)
Review
Trypanosoma cruzi, and the T. brucei group of parasites cause neglected diseases that affect millions of people around the world. These unicellular microorganisms have complex life cycles involving an insect vector and a mammalian host. Both groups of pathogens possess an inositol 1,4,5-trisphosphate (IP)/diacylglycerol (DAG) signaling pathway, and an IP receptor, but with lineage-specific adaptations that make them different from their mammalian counterparts. The phospholipase C (PLC), which hydrolyzes phosphatidyl inositol 4,5-bisphosphate (PIP) to IP is N-terminally myristoylated and palmitoylated. Acidocalcisomes, which are lysosome-related organelles rich in polyphosphate, are the main intracellular Ca stores. The inositol 1,4,5-trisphosphate receptor (IPR) localizes to acidocalcisomes instead of the endoplasmic reticulum. The trypanosome IPR is stimulated by luminal phosphate and pyrophosphate, which are hydrolysis products of polyphosphate (polyP), and inhibited by tripolyphosphate (polyP), which is the most abundant polyP in acidocalcisomes. Ca signaling is important for host cell invasion and differentiation and to maintain cellular bioenergetics.
Topics: Animals; Calcium Signaling; Endoplasmic Reticulum; Humans; Inositol 1,4,5-Trisphosphate Receptors; Life Cycle Stages; Trypanosoma; Type C Phospholipases
PubMed: 33421534
DOI: 10.1016/j.bbamcr.2021.118947 -
ACS Infectious Diseases Jun 2021We now describe the physicochemical profiling, ADME, and antiparasitic activity of eight ,-diarylureas to assess their potential as a broad-spectrum antiprotozoal...
We now describe the physicochemical profiling, ADME, and antiparasitic activity of eight ,-diarylureas to assess their potential as a broad-spectrum antiprotozoal chemotype. Chromatographic LogD values ranged from 2.5 to 4.5; kinetic aq. solubilities were ≤6.3 μg/mL, and plasma protein binding ranged from 95 to 99%. All of the compounds had low intrinsic clearance values in human, but not mouse, liver microsomes. Although no ,-diarylurea had submicromolar potency against , two had submicromolar potencies against and , and five had submicromolar potencies against . appeared to be the most susceptible to growth inhibition by this compound series. Most of the ,-diarylureas had antiprotozoal selectivities ≥10. One ,-diarylurea had demonstrable activity in mouse models of malaria and toxoplasmosis.
Topics: Animals; Antiprotozoal Agents; Leishmania donovani; Mice; Trypanosoma brucei rhodesiense; Trypanosoma cruzi; Urea
PubMed: 33971090
DOI: 10.1021/acsinfecdis.1c00135 -
Journal of Bacteriology Aug 1977Polyamines were determined by n-butanol extraction and thin-layer chromatography in four trypanosomatids: Trypanosoma brucei (rat infection) and cultures of Crithidia... (Comparative Study)
Comparative Study
Polyamines were determined by n-butanol extraction and thin-layer chromatography in four trypanosomatids: Trypanosoma brucei (rat infection) and cultures of Crithidia fasciculata, Leptomonas sp., and Trypanosoma mega. All had putrescine and spermidine but no detectable spermine. Putrescine and spermidine levels were quantitated for extracts of leptomonas during the normal growth cycle. Spermidine values peaked 18 h before peak cell populations. Spermidine-putrescine ratios for all organisms were related to the presumed phylogeny of the group.
Topics: Animals; Eukaryota; Putrescine; Spermidine; Spermine; Trypanosoma; Trypanosoma brucei brucei
PubMed: 885842
DOI: 10.1128/jb.131.2.657-661.1977 -
ELife May 2023African trypanosomes proliferate as bloodstream forms (BSFs) and procyclic forms in the mammal and tsetse fly midgut, respectively. This allows them to colonise the host...
African trypanosomes proliferate as bloodstream forms (BSFs) and procyclic forms in the mammal and tsetse fly midgut, respectively. This allows them to colonise the host environment upon infection and ensure life cycle progression. Yet, understanding of the mechanisms that regulate and drive the cell replication cycle of these forms is limited. Using single-cell transcriptomics on unsynchronised cell populations, we have obtained high resolution cell cycle regulated (CCR) transcriptomes of both procyclic and slender BSF without prior cell sorting or synchronisation. Additionally, we describe an efficient freeze-thawing protocol that allows single-cell transcriptomic analysis of cryopreserved . Computational reconstruction of the cell cycle using periodic pseudotime inference allowed the dynamic expression patterns of cycling genes to be profiled for both life cycle forms. Comparative analyses identify a core cycling transcriptome highly conserved between forms, as well as several genes where transcript levels dynamics are form specific. Comparing transcript expression patterns with protein abundance revealed that the majority of genes with periodic cycling transcript and protein levels exhibit a relative delay between peak transcript and protein expression. This work reveals novel detail of the CCR transcriptomes of both forms, which are available for further interrogation via an interactive webtool.
Topics: Trypanosoma; Single-Cell Gene Expression Analysis; Cryopreservation; RNA, Protozoan; Protozoan Proteins
PubMed: 37166108
DOI: 10.7554/eLife.86325 -
Mathematical Biosciences and... Jun 2022In this paper, an insect-parasite-host model with logistic growth of triatomine bugs is formulated to study the transmission between hosts and vectors of the Chagas...
In this paper, an insect-parasite-host model with logistic growth of triatomine bugs is formulated to study the transmission between hosts and vectors of the Chagas disease by using dynamical system approach. We derive the basic reproduction numbers for triatomine bugs and as two thresholds. The local and global stability of the vector-free equilibrium, parasite-free equilibrium and parasite-positive equilibrium is investigated through the derived two thresholds. Forward bifurcation, saddle-node bifurcation and Hopf bifurcation are proved analytically and illustrated numerically. We show that the model can lose the stability of the vector-free equilibrium and exhibit a supercritical Hopf bifurcation, indicating the occurrence of a stable limit cycle. We also find it unlikely to have backward bifurcation and Bogdanov-Takens bifurcation of the parasite-positive equilibrium. However, the sustained oscillations of infected vector population suggest that will persist in all the populations, posing a significant challenge for the prevention and control of Chagas disease.
Topics: Animals; Chagas Disease; Disease Vectors; Rhodnius; Trypanosoma cruzi; Trypanosoma rangeli
PubMed: 35801473
DOI: 10.3934/mbe.2022393 -
Parasitology Sep 2022Bats are mammalian hosts to a large diversity of eukaryotic protozoan blood parasites, including different genera of haemosporidians and diverse species of trypanosomes....
Bats are mammalian hosts to a large diversity of eukaryotic protozoan blood parasites, including different genera of haemosporidians and diverse species of trypanosomes. Phylogenetic studies suggest that bats, particularly in Africa, have played an important role in the evolutionary histories of these parasite groups. However, our understanding of the diversity and distribution of chiropteran haemosporidians and trypanosomes in Africa remains tenuous. We investigated the prevalence and phylogenetic relationships of the blood parasites in different bat species in Northern Nigeria using molecular methods. A low prevalence of parasites was detected in a potentially rare host species, the African straw-coloured fruit bat () confirming yet another fruit bat species in the diverse range of African bat hosts. Trypanosome infections were identified in 3 different bat species. The trypanosomes of cf. were recovered as a distinct lineage that is related to , a species which is closely related to and cf. bats were infected with trypanosomes that are related to the distinct lineage of cf. parasites. Further, 2 different lineages of trypanosomes in bats share highest nucleotide identities with and a group of sp. parasites that are closely related to cf. and , respectively. The findings of this study confirm the notion that trypanosomes of African bats are phylogenetically diverse and that African bats might harbour a variety of yet undescribed trypanosome species.
Topics: Animals; Chiroptera; Haemosporida; Nigeria; Nucleotides; Parasitic Diseases; Phylogeny; Trypanosoma; Trypanosoma cruzi
PubMed: 35822266
DOI: 10.1017/S0031182022000890 -
Parasitology Sep 2021The passage of mRNAs through the nuclear pores into the cytoplasm is essential in all eukaryotes. For regulation, mRNA export is tightly connected to the full machinery... (Review)
Review
The passage of mRNAs through the nuclear pores into the cytoplasm is essential in all eukaryotes. For regulation, mRNA export is tightly connected to the full machinery of nuclear mRNA processing, starting at transcription. Export competence of pre-mRNAs gradually increases by both transient and permanent interactions with multiple RNA processing and export factors. mRNA export is best understood in opisthokonts, with limited knowledge in plants and protozoa. Here, I review and compare nuclear mRNA processing and export between opisthokonts and Trypanosoma brucei. The parasite has many unusual features in nuclear mRNA processing, such as polycistronic transcription and trans-splicing. It lacks several nuclear complexes and nuclear-pore-associated proteins that in opisthokonts play major roles in mRNA export. As a consequence, trypanosome mRNA export control is not tight and export can even start co-transcriptionally. Whether trypanosomes regulate mRNA export at all, or whether leakage of immature mRNA to the cytoplasm is kept to a low level by a fast kinetics of mRNA processing remains to be investigated. mRNA export had to be present in the last common ancestor of eukaryotes. Trypanosomes are evolutionary very distant from opisthokonts and a comparison helps understanding the evolution of mRNA export.
Topics: Eukaryota; RNA, Messenger; RNA, Nuclear; Trypanosoma
PubMed: 33461637
DOI: 10.1017/S0031182021000068 -
Seminars in Cell & Developmental Biology May 2011Methylglyoxal is a toxic by-product of glycolysis and other metabolic pathways. In mammalian cells, the principal route for detoxification of this reactive metabolite is... (Review)
Review
Methylglyoxal is a toxic by-product of glycolysis and other metabolic pathways. In mammalian cells, the principal route for detoxification of this reactive metabolite is via the glutathione-dependent glyoxalase pathway forming d-lactate, involving lactoylglutathione lyase (GLO1; EC 4.4.1.5) and hydroxyacylglutathione hydrolase (GLO2; EC 3.2.1.6). In contrast, the equivalent enzymes in the trypanosomatid parasites Trypanosoma cruzi and Leishmania spp. show >200-fold selectivity for glutathionylspermidine and trypanothione over glutathione and are therefore sensu stricto lactoylglutathionylspermidine lyases (EC 4.4.1.-) and hydroxyacylglutathionylspermidine hydrolases (EC 3.2.1.-). The unique substrate specificity of the parasite glyoxalase enzymes can be directly attributed to their unusual active site architecture. The African trypanosome differs from these parasites in that it lacks GLO1 and converts methylglyoxal to l-lactate rather than d-lactate. Since Trypanosoma brucei is the most sensitive of the trypanosomatids to methylglyoxal toxicity, the absence of a complete and functional glyoxalase pathway in these parasites is perplexing. Alternative routes of methylglyoxal detoxification in T. brucei are discussed along with the potential of exploiting trypanosomatid glyoxalase enzymes as targets for anti-parasitic chemotherapy.
Topics: Animals; Antiprotozoal Agents; Humans; Lactoylglutathione Lyase; Leishmania; Pyruvaldehyde; Thiolester Hydrolases; Trypanosoma
PubMed: 21310261
DOI: 10.1016/j.semcdb.2011.02.001