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https://www.readbyqxmd.com/read/28807106/developmental-adaptations-of-trypanosome-motility-to-the-tsetse-fly-host-environments-unravel-a-multifaceted-in-vivo-microswimmer-system
#1
Sarah Schuster, Timothy Krüger, Ines Subota, Sina Thusek, Brice Rotureau, Andreas Beilhack, Markus Engstler
The highly motile and versatile protozoan pathogen Trypanosoma brucei undergoes a complex life cycle in the tsetse fly. Here we introduce the host insect as an expedient model environment for microswimmer research, as it allows examination of microbial motion within a diversified, secluded and yet microscopically tractable space. During their week-long journey through the different microenvironments of the fly´s interior organs, the incessantly swimming trypanosomes cross various barriers and confined surroundings, with concurrently occurring major changes of parasite cell architecture...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28804485/transcriptional-profiling-of-midguts-prepared-from-trypanosoma-t-congolense-positive-glossina-palpalis-palpalis-collected-from-two-distinct-cameroonian-foci-coordinated-signatures-of-the-midguts-remodeling-as-t-congolense-supportive-niches
#2
Jean M Tsagmo Ngoune, Flobert Njiokou, Béatrice Loriod, Ginette Kame-Ngasse, Nicolas Fernandez-Nunez, Claire Rioualen, Jacques van Helden, Anne Geiger
Our previous transcriptomic analysis of Glossina palpalis gambiensis experimentally infected or not with Trypanosoma brucei gambiense aimed to detect differentially expressed genes (DEGs) associated with infection. Specifically, we selected candidate genes governing tsetse fly vector competence that could be used in the context of an anti-vector strategy, to control human and/or animal trypanosomiasis. The present study aimed to verify whether gene expression in field tsetse flies (G. p. palpalis) is modified in response to natural infection by trypanosomes (T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28800584/expression-of-the-rna-binding-protein-rbp10-promotes-the-bloodstream-form-differentiation-state-in-trypanosoma-brucei
#3
Elisha Mugo, Christine Clayton
In nearly all eukaryotes, cellular differentiation is governed by changes in transcription, and stabilized by chromatin and DNA modification. Gene expression control in the pathogen Trypanosoma brucei, in contrast, relies almost exclusively on post-transcriptional mechanisms, so RNA binding proteins must assume the burden that is usually borne by transcription factors. T. brucei multiply in the blood of mammals as bloodstream forms, and in the midgut of Tsetse flies as procyclic forms. We show here that a single RNA-binding protein, RBP10, promotes the bloodstream-form trypanosome differentiation state...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28792090/distinct-activation-mechanisms-trigger-the-trypanocidal-activity-of-dna-damaging-prodrugs
#4
Emma Louise Meredith, Ambika Kumar, Aya Konno, Joanna Szular, Sam Alsford, Karin Seifert, David Horn, Shane R Wilkinson
Quinone-based compounds have been exploited to treat infectious diseases and cancer, with such chemicals often functioning as inhibitors of key metabolic pathways or as prodrugs. Here, we screened an aziridinyl-1,4-benzoquinone (ABQ) library against the causative agents of trypanosomiasis, and cutaneous leishmaniasis, identifying several potent structures that exhibited EC50 values of <100 nM. However, these compounds also displayed significant toxicity towards mammalian cells indicating that they are not suitable therapies for systemic infections...
August 9, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28783594/antigenic-characterization-of-52-55kda-protein-isolated-from-trypanosoma-evansi-and-its-application-in-detection-of-equine-trypanosomosis
#5
S C Yadav, Ritesh Kumar, Jaideep Kumar, Meetali Singh, B C Bera, Rajender Kumar, U Tatu, Kanika Tehri
Trypanosoma evansi is a haemo-protozoan parasite responsible for the disease surra, an economically important disease of wide range of domestic and wild animals. The present diagnostic methods using soluble antigens have inherent problems like lack of standardized and reproducible antigens, as well as ethical issues. This entails further efforts for search of defined antigenic molecules with satisfying sensitivity and specificity for sero-epidemiology of trypanosomosis. In present investigation, we have identified and purified 52-55kDa immuno-dominant protein cluster in molecular mass ranges by preparatory SDS-PAGE methods from T...
August 1, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28780409/antiparasitic-activity-against-trypanosomatid-diseases-and-novel-metal-complexes-derived-from-the-first-time-characterized-5-phenyl-1-2-4-triazolo-1-5-a-pyrimidi-7-4h-one
#6
J M Méndez-Arriaga, G M Esteban-Parra, M J Juárez, A Rodríguez-Diéguez, M Sánchez-Moreno, J Isac-García, J M Salas
A serie of isostructural complexes with general formula [M(ftpO)2(H2O)4] have been obtained from reaction between the first time characterized triazolopyrimidine derivative 5-phenyl-1,2,4-triazolo[1,5-a]pyrimidi-7(4H)-one (HftpO) (1) and first row transition nitrates (M=Cu (2), Co (3), Ni (4) and Zn (5)). A copper complex with formula [Cu(HftpO)2(NO3)2(H2O)2]·H2O (6) was also isolated. HftpO and their metal complexes have been characterized by spectroscopic and thermal analysis and their crystal structures have been solved by X-ray diffraction methods...
July 29, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28766862/inhibition-of-protein-protein-interactions-new-options-for-developing-drugs-against-neglected-tropical-diseases
#7
Thorsten Berg
Wake up! Sleeping sickness and Chagas disease are neglected tropical diseases caused by trypanosome infections. Small molecules that disrupt a crucial protein-protein interaction in the parasites offer a new approach to drug development for these diseases.
August 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28763686/in-silico-molecular-docking-studies-of-new-potential-4-phthalazinyl-hydrazones-on-selected-trypanosoma-cruzi-and-leishmania-enzyme-targets
#8
Angel H Romero, Simón E López
Recently, a series of 4-phthalazinyl-hydrazones under its E-configuration have exhibited excellent in vitro antichagasic and antileishmanial profiles. Preliminary assays on both parasites suggested that the most active derivatives act through oxidative and nitrosative stress mechanisms; however, their exact mode of actions as anti-trypanosomal and anti-leishmanial agents have not been completely elucidated. This motivated to perform a molecular docking study on essential trypanosomatid enzymes such as superoxide dismutase (SOD), trypanothione reductase (TryR), cysteine-protease (CP) and pteridine reductase 1 (PTR1)...
July 19, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28760415/surface-glycans-a-therapeutic-opportunity-for-kinetoplastid-diseases
#9
REVIEW
Víctor M Castillo-Acosta, Jan Balzarini, Dolores González-Pacanowska
Trypanosomal diseases are in need of innovative therapies that exploit novel mechanisms of action. The cell surface of trypanosomatid parasites is characterized by a dense coat of glycoconjugates with important functions in host cell recognition, immune evasion, infectivity, and cell function. The nature of parasite surface glycans is highly dynamic and changes during differentiation and in response to different stimuli through the action of glycosyltransferases and glycosidases. Here we propose a new approach to antiparasitic drug discovery that involves the use of carbohydrate-binding agents that bind specifically to cell-surface glycans, giving rise to cytotoxic events and parasite death...
July 28, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28756490/age-specific-patterns-of-infection-with-haemosporidians-and-trypanosomes-in-a-warbler-implications-for-sexual-selection
#10
Corey R Freeman-Gallant, Conor C Taff
Although the selective loss of individuals susceptible to disease can favor the evolution of female preference for older males, the interrelationship between age, infection, longevity, and mating success remains poorly characterized in natural populations. In a longitudinal study of 61 male common yellowthroats (Geothlypis trichas), we found that the probability of infection with hematozoa increased as males aged from 1 to 5 years. Despite a significant, negative association between infection and longevity that partially masked age-effects, the odds that a male was infected with Trypanosoma, Plasmodium, or Leucocytozoon increased 71-212% per year...
July 29, 2017: Oecologia
https://www.readbyqxmd.com/read/28752916/discovery-and-genomic-analyses-of-hybridization-between-divergent-lineages-of-trypanosoma-congolense-causative-agent-of-animal-african-trypanosomiasis
#11
Eliane Tihon, Hideo Imamura, Jean-Claude Dujardin, Jan Van Den Abbeele, Frederik Van den Broeck
Hybrid populations and introgressive hybridization remain poorly documented in pathogenic microorganisms, as such that genetic exchange has been argued to play a minor role in their evolution. Recent work demonstrated the existence of hybrid microsatellite profiles in Trypanosoma congolense, a parasitic protozoan with detrimental effects on livestock productivity in sub-Saharan Africa. Here we present the first population genomic study of T. congolense, revealing a remarkable number of Single Nucleotide Polymorphisms (SNPs), small insertions/deletions (indels) and gene deletions among 56 parasite genomes from ten African countries...
July 28, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28746445/bat-trypanosomes-from-tapaj%C3%A3-s-arapiuns-extractive-reserve-in-brazilian-amazon
#12
Bruno Bernal Szpeiter, Juliana Isabel Giuli da Silva Ferreira, Francisco Flávio Vieira de Assis, Felipe Nascimento Stelmachtchuk, Kleber da Cunha Peixoto, Daniel Ajzenberg, Antonio Humberto Hammad Minervino, Solange Maria Gennari, Arlei Marcili
Trypanosoma comprises flagellates able to infect several mammalian species and is transmitted by several groups of invertebrates. The order Chiroptera can be infected by the subgenera Herpetosoma, Schizotrypanum, Megatrypanum and Trypanozoon. In this study, we described the diversity of bat trypanosomes and inferred phylogenetic relationships among the trypanosomes from bats caught in Tapajós-Arapiuns Extractive Reserve (Resex) in Pará state. Trypanosomes from bats were isolated by means of hemoculture, and the molecular phylogeny was based on the trypanosome barcode (SSUrDNA V7V8 variable region)...
April 2017: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
https://www.readbyqxmd.com/read/28742275/the-proteome-and-transcriptome-of-the-infectious-metacyclic-form-of-trypanosoma-brucei-define-quiescent-cells-primed-for-mammalian-invasion
#13
Romain Christiano, Nikolay G Kolev, Huafang Shi, Elisabetta Ullu, Tobias C Walther, Christian Tschudi
The infectious metacyclic forms of Trypanosoma brucei result from a complex development in the tsetse fly vector. When they infect mammals, they cause African sleeping sickness in humans. Due to scarcity of biological material and difficulties of the tsetse fly as an experimental system, very limited information is available concerning the gene expression profile of metacyclic forms. We used an in vitro system based on expressing the RNA binding protein 6 to obtain infectious metacyclics and determined their protein and mRNA repertoires by mass-spectrometry (MS) based proteomics and mRNA sequencing (RNA-Seq) in comparison to non-infectious procyclic trypanosomes...
July 25, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28739368/andrographolide-induces-oxidative-stress-dependent-cell-death-in-unicellular-protozoan-parasite-trypanosoma-brucei
#14
Malabika Banerjee, Debaprasad Parai, Pranab Dhar, Manab Roy, Rajib Barik, Subrata Chattopadhyay, Samir Kumar Mukherjee
African sleeping sickness is a parasitic disease in humans and livestock caused by Trypanosoma brucei throughout sub-Saharan Africa. Absence of appropriate vaccines and prevalence of drug resistance proclaim that a new way of therapeutic interventions is essential against African trypanosomiasis. In the present study, we have looked into the effect of andrographolide (andro), a diterpenoid lactone from Andrographis paiculata on Trypanosoma brucei PRA 380. Although andro has been recognized as a promosing anti-cancer drug, its usefulness against Trypanosoma spp remained unexplored...
July 21, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28733685/trypanosoma-brucei-growth-control-by-tnf-in-mammalian-host-is-independent-of-the-soluble-form-of-the-cytokine
#15
Gilles Vanwalleghem, Yannick Morias, Alain Beschin, David E Szymkowski, Etienne Pays
Infection of C57Bl/6 mice by pleomorphic African trypanosomes Trypanosoma brucei and T. congolense is characterized by parasitemia waves coupled with the production of systemic levels of TNF. This cytokine is known to control T. brucei growth, but also to contribute to tissue damage, shortening the survival time of infected mice. Using a dominant-negative version of TNF to discriminate between the effects of the membrane-form versus the soluble form of TNF, we show that the second form is involved in neither parasite control nor induction of liver injury...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733613/rnai-screening-identifies-trypanosoma-brucei-stress-response-protein-kinases-required-for-survival-in-the-mouse
#16
Fernando Fernandez-Cortes, Tiago D Serafim, Jonathan M Wilkes, Nathaniel G Jones, Ryan Ritchie, Richard McCulloch, Jeremy C Mottram
Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729055/novel-1-2-dihydroquinazolin-2-ones-design-synthesis-and-biological-evaluation-against-trypanosoma-brucei
#17
ThanhTruc Pham, Madeline Walden, Christopher Butler, Rosario Diaz-Gonzalez, Guiomar Pérez-Moreno, Gloria Ceballos-Pérez, Veronica Gomez-Pérez, Raquel García-Hernández, Henry Zecca, Emma Krakoff, Brian Kopec, Ogar Ichire, Caden Mackenzie, Marika Pitot, Luis Miguel Ruiz, Francisco Gamarro, Dolores González-Pacanowska, Miguel Navarro, Amy B Dounay
In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability...
July 11, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28727848/the-nuclear-proteome-of-trypanosoma-brucei
#18
Carina Goos, Mario Dejung, Christian J Janzen, Falk Butter, Susanne Kramer
Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host...
2017: PloS One
https://www.readbyqxmd.com/read/28727769/small-subunit-ribosomal-metabarcoding-reveals-extraordinary-trypanosomatid-diversity-in-brazilian-bats
#19
Maria Augusta Dario, Ricardo Moratelli, Philipp Schwabl, Ana Maria Jansen, Martin S Llewellyn
BACKGROUND: Bats are a highly successful, globally dispersed order of mammals that occupy a wide array of ecological niches. They are also intensely parasitized and implicated in multiple viral, bacterial and parasitic zoonoses. Trypanosomes are thought to be especially abundant and diverse in bats. In this study, we used 18S ribosomal RNA metabarcoding to probe bat trypanosome diversity in unprecedented detail. METHODOLOGY/PRINCIPAL FINDINGS: Total DNA was extracted from the blood of 90 bat individuals (17 species) captured along Atlantic Forest fragments of Espírito Santo state, southeast Brazil...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28724794/apol1-variants-change-c-terminal-conformational-dynamics-and-binding-to-snare-protein-vamp8
#20
Sethu M Madhavan, John F O'Toole, Martha Konieczkowski, Laura Barisoni, David B Thomas, Santhi Ganesan, Leslie A Bruggeman, Matthias Buck, John R Sedor
APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor. VAMP8 colocalizes with APOL1 in the podocyte, and the APOL1:VAMP8 interaction was confirmed biochemically and with surface plasmon resonance...
July 20, 2017: JCI Insight
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