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Srinivasan Ramakrishnan, Beejan Asady, Roberto Docampo
Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such contact sites in Trypanosoma brucei . In mammalian cells, endoplasmic reticulum-mitochondria contact sites facilitate mitochondrial uptake of Ca2+ released by the ER-located inositol 1,4,5-trisphosphate receptor (InsP₃R)...
March 22, 2018: Pathogens
Evelyn Rogerson, Julien Pelletier, Alvaro Acosta-Serrano, Clair Rose, Sarah Taylor, Scott Guimond, Marcelo Lima, Mark Skidmore, Edwin Yates
Tsetse flies are the principal insect vectors of African trypanosomes -sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans , is host to the parasite, Trypanosoma brucei , a major cause of African trypanosomiasis. Precise details of the life cycle have yet to be established, but the parasite life cycle involves crossing the insect peritrophic matrix (PM). The PM consists of the polysaccharide chitin, several hundred proteins, and both glycosamino- and galactosaminoglycan (GAG) polysaccharides...
March 19, 2018: Pathogens
Muluken Yayeh, Shimelis Dagnachew, Meseret Tilahun, Achenef Melaku, Tadegegn Mitiku, Mohamed Yesuf, Zewdu Seyoum, Habtamu Kefyalew
The current study was undertaken from December 2015 to May 2016 with the aim of determining and comparing the pathogenicity and response to diminazene aceturate (DA) and isometamidium chloride (ISM) treatment in experimentally infected mice with trypanosome isolates from Jawi and Birsheleko areas of northwest Ethiopia. A total of 42 mice were used for the experiment. These mice were randomly assigned in to 7 groups of 6 mice per group. Three of the groups (Group 1, 4 and 5) were inoculated with trypanosome isolated from Jawi and three other groups (Group-2, 6 and 7) were inoculated with trypanosome isolated from Birsheleko and the remaining one group (Group 3) was negative control...
February 2018: Heliyon
Fabricio Castro Machado, Caio Haddad Franco, Jose Vitorino Dos Santos Neto, Karina Luiza Dias-Teixeira, Carolina Borsoi Moraes, Ulisses Gazos Lopes, Bertal Huseyin Aktas, Sergio Schenkman
Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T...
March 20, 2018: Scientific Reports
Thomas W M Crozier, Michele Tinti, Richard J Wheeler, Tony Ly, Michael A J Ferguson, Angus I Lamond
We describe a single-step centrifugal elutriation method to produce synchronous G1-phase procyclic trypanosomes at a scale amenable for proteomic analysis of the cell cycle. Using ten-plex tandem mass tag (TMT) labelling and mass spectrometry (MS)-based proteomics technology, the expression levels of 5,325 proteins were quantified across the cell cycle in this parasite. Of these, 384 proteins were classified as cell-cycle regulated and subdivided into nine clusters with distinct temporal regulation. These groups included many known cell cycle regulators in trypanosomes, which validates the approach...
March 19, 2018: Molecular & Cellular Proteomics: MCP
Marina Bentivoglio, Giuseppe Bertini
Rijo-Ferreira et al. report alterations of circadian rhythmicity at the behavioral, tissue, cellular, and molecular levels in mice after Trypanosoma brucei infection, showing that targeting cell clocks is a specific feature of these parasites. Thus, African trypanosomes cause a severe disease by disrupting time-keeping mechanisms and their synchrony.
March 16, 2018: Trends in Parasitology
Godwin U Ebiloma, Evangelos Katsoulis, John O Igoli, Alexander I Gray, Harry P De Koning
Natural products have made remarkable contributions to drug discovery and therapy. In this work we exploited various biochemical approaches to investigate the mode of action of 16-α-hydroxy-cleroda-3,13 (14)-Z-dien-15,16-olide (HDK-20), which we recently isolated from Polyalthia longifolia, on Trypanosoma brucei bloodstream trypomastigotes. HDK20 at concentrations ≥ EC50 (0.4 μg/ml) was trypanocidal, with its effect irreversible after only a brief exposure time (<1 h). Fluorescence microscopic assessment of DNA configuration revealed severe cell cycle defects after 8 h of incubation with the compound, the equivalent of a single generation time...
March 15, 2018: Scientific Reports
Oneida Espinosa-Álvarez, Paola A Ortiz, Luciana Lima, André G Costa-Martins, Myrna G Serrano, Stephane Herder, Gregory A Buck, Erney P Camargo, Patrick B Hamilton, Jamie R Stevens, Marta M G Teixeira
Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader (SL) RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T...
March 12, 2018: International Journal for Parasitology
Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Janaina de Freitas Nascimento, Steven Kelly, Jack Sunter, Mark Carrington
Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs...
March 15, 2018: ELife
Sara Silva Pereira, Andrew P Jackson
BACKGROUND: Trypanosomatid parasites such as Trypanosoma spp. and Leishmania spp. are a major source of infectious disease in humans and domestic animals worldwide. Fundamental to the host-parasite interactions of these potent pathogens are their cell surfaces, which are highly decorated with glycosylated proteins and other macromolecules. Trypanosomatid genomes contain large multi-copy gene families encoding UDP-dependent glycosyltransferases (UGTs), the primary role of which is cell-surface decoration...
March 14, 2018: BMC Evolutionary Biology
Claudia Laperchia, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Tiziana Cotrufo, Marina Bentivoglio
Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei ( T. b .) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T...
2018: Frontiers in Neuroanatomy
Colleen Edith Archer, M Corrie Schoeman, Christopher Charles Appleton, Samson Mukaratirwa, Karen J Hope, Glenda Beverly Matthews
This study investigated associations between Trypanosoma lewisi; Xenopsylla cheopis, a common cyclical vector of T. lewisi; Polyplax spinulosa, a reported mechanical vector; and Laelaps ecidnina and L. lamborni, two rodent mites of Rattus norvegicus in Durban. Three hundred and seventy nine R. norvegicus were live-trapped at 48 sites in 4 locality types of Durban during a one year period. Rats were euthanized, cardiac blood was taken to check for hemoparasites and ectoparasites were removed for identification...
March 13, 2018: Journal of Parasitology
Hanako Hayashi, Bungo Akiyoshi
Kinetoplastids have a nucleus that contains the nuclear genome and a kinetoplast that contains the mitochondrial genome. These single-copy organelles must be duplicated and segregated faithfully to daughter cells at each cell division. In Trypanosoma brucei , although duplication of both organelles starts around the same time, segregation of the kinetoplast precedes that of the nucleus. Cytokinesis subsequently takes place so that daughter cells inherit a single copy of each organelle. Very little is known about the molecular mechanism that governs the timing of these events...
March 12, 2018: Biology Open
E Quintero-Troconis, N Buelvas, C Carrasco-López, M R Domingo-Sananes, L González-González, R Ramírez-Molina, L Osorio, A Lobo-Rojas, A J Cáceres, P A Michels, H Acosta, W Quiñones, J L Concepción
Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain...
March 9, 2018: Biochimica et Biophysica Acta
I Matetovici, J Van Den Abbeele
Thioester-containing proteins (TEPs) are conserved proteins with a role in innate immune immunity. In the current study, we characterized the TEP family in the genome of six tsetse fly species (Glossina spp.). Tsetse flies are the biological vectors of several African trypanosomes, which cause sleeping sickness in humans or nagana in livestock. The analysis of the tsetse TEP sequences revealed information about their structure, evolutionary relationships and expression profiles under both normal and trypanosome infection conditions...
March 12, 2018: Insect Molecular Biology
Carolina R Marotta, Priscilla N Dos Santos, Matheus D Cordeiro, Juliana Helena Da S Barros, Lesley Bell-Sakyi, Adivaldo H Fonseca
Parasites of the genus Trypanosoma are microorganisms that display wide morphological, biological and genetic variability. Here we present the first description of an isolate of the genus Trypanosoma naturally infecting the tick Amblyomma brasiliense . The ticks were collected from a specimen of Tayassu pecari (Queixada, white-lipped peccary) from the Itatiaia National Park, Itatiaia, Rio de Janeiro, Brazil. The isolate was characterised by molecular, morphometric and biological analyses. A Trypanosoma culture was isolated from crushed nymphal and adult ticks, propagated in the tick cell line IDE8 and maintained in L15B culture medium, incubated at 32 °C...
2018: Parasitology Open
Benoit Stijlemans, Patrick De Baetselier, Stefan Magez, Jo A Van Ginderachter, Carl De Trez
African trypanosomosis (AT) is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS), involving classically activated macrophages (i...
2018: Frontiers in Immunology
Jennifer M Holden, Ludek Koreny, Samson Obado, Alexander V Ratushny, Wei-Ming Chen, Jean-Mathieu Bart, Miguel Navarro, Brian T Chait, John D Aitchison, Michael P Rout, Mark C Field
Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions, and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores and parts of the NPCs...
March 1, 2018: Molecular Biology of the Cell
Chiara Tesoriero, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Marina Bentivoglio
Trypanosoma brucei ( T. b. ) gambiense is the parasite subspecies responsible for most reported cases of human African trypanosomiasis (HAT) or sleeping sickness. This severe infection leads to characteristic disruption of the sleep-wake cycle, recalling attention on the circadian timing system. Most animal models of the disease have been hitherto based on infection of laboratory rodents with the T. b. brucei subspecies, which is not infectious to humans. In these animal models, functional, rather than structural, alterations of the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), have been reported...
2018: Frontiers in Neuroanatomy
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