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Trypanosomatids

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https://www.readbyqxmd.com/read/28338335/stress-induced-protein-s-glutathionylation-and-s-trypanothionylation-in-african-trypanosomes-a-quantitative-redox-proteome-and-thiol-analysis
#1
Kathrin Ulrich, Caroline Finkenzeller, Sabine Merker, Federico Rojas, Keith Matthews, Thomas Ruppert, R Luise Krauth-Siegel
AIMS: Trypanosomatids have a unique trypanothione-based thiol redox metabolism. The parasite-specific dithiol is synthesized from glutathione and spermidine, with glutathionylspermidine as intermediate catalyzed by trypanothione synthetase. In this study, we address the oxidative stress response of African trypanosomes with special focus on putative protein S-thiolation. RESULTS: Challenging bloodstream Trypanosoma brucei with diamide, H2O2 or hypochlorite results in distinct levels of reversible overall protein S-thiolation...
March 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28328988/molecular-mechanisms-of-thermal-resistance-of-the-insect-trypanosomatid-crithidia-thermophila
#2
Aygul Ishemgulova, Anzhelika Butenko, Lucie Kortišová, Carolina Boucinha, Anastasiia Grybchuk-Ieremenko, Karina A Morelli, Martina Tesařová, Natalya Kraeva, Danyil Grybchuk, Tomáš Pánek, Pavel Flegontov, Julius Lukeš, Jan Votýpka, Márcio Galvão Pavan, Fred R Opperdoes, Viktoria Spodareva, Claudia M d'Avila-Levy, Alexei Yu Kostygov, Vyacheslav Yurchenko
In the present work, we investigated molecular mechanisms governing thermal resistance of a monoxenous trypanosomatid Crithidia luciliae thermophila, which we reclassified as a separate species C. thermophila. We analyzed morphology, growth kinetics, and transcriptomic profiles of flagellates cultivated at low (23°C) and elevated (34°C) temperature. When maintained at high temperature, they grew significantly faster, became shorter, with genes involved in sugar metabolism and mitochondrial stress protection significantly upregulated...
2017: PloS One
https://www.readbyqxmd.com/read/28319176/insight-into-the-mechanism-of-action-of-temporin-sha-a-new-broad-spectrum-antiparasitic-and-antibacterial-agent
#3
Zahid Raja, Sonia André, Feten Abbassi, Vincent Humblot, Olivier Lequin, Tahar Bouceba, Isabelle Correia, Sandra Casale, Thierry Foulon, Denis Sereno, Bruno Oury, Ali Ladram
Antimicrobial peptides (AMPs) are promising drugs to kill resistant pathogens. In contrast to bacteria, protozoan parasites, such as Leishmania, were little studied. Therefore, the antiparasitic mechanism of AMPs is still unclear. In this study, we sought to get further insight into this mechanism by focusing our attention on temporin-SHa (SHa), a small broad-spectrum AMP previously shown to be active against Leishmania infantum. To improve activity, we designed analogs of SHa and compared the antibacterial and antiparasitic mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28282886/chroman-4-one-derivatives-targeting-pteridine-reductase-1-and-showing-anti-parasitic-activity
#4
Flavio Di Pisa, Giacomo Landi, Lucia Dello Iacono, Cecilia Pozzi, Chiara Borsari, Stefania Ferrari, Matteo Santucci, Nuno Santarem, Anabela Cordeiro-da-Silva, Carolina B Moraes, Laura M Alcantara, Vanessa Fontana, Lucio H Freitas-Junior, Sheraz Gul, Maria Kuzikov, Birte Behrens, Ina Pöhner, Rebecca C Wade, Maria Paola Costi, Stefano Mangani
Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1-TbPTR1 and Leishmania major-LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved...
March 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28258618/differences-in-the-detection-of-brdu-edu-incorporation-assays-alter-the-calculation-for-g1-s-and-g2-phases-of-the-cell-cycle-in-trypanosomatids
#5
Marcelo Santos da Silva, Paula Andrea Marin Muñoz, Hugo Aguirre Armelin, Maria Carolina Elias
Trypanosomatids are the etiologic agents of various infectious diseases in humans. They diverged early during eukaryotic evolution and have attracted attention as peculiar models for evolutionary and comparative studies. Here, we show a meticulous study comparing the incorporation and detection of the thymidine analogs BrdU and EdU in Leishmania amazonensis, Trypanosoma brucei, and Trypanosoma cruzi to monitor their DNA replication. We used BrdU- and EdU-incorporated parasites with the respective standard detection approaches: Indirect Immunofluorescence to detect BrdU after standard denaturation (2 M HCl) and "click" chemistry to detect EdU...
March 4, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28246372/a-novel-stage-specific-glycosomal-nucleoside-diphosphate-kinase-from-trypanosoma-cruzi
#6
Maria de Los Milagros Camara, Leon Bouvier, Chantal Reigada, Fabio A Digirolamo, Melisa Saye, Claudio A Pereira
Nucleoside diphosphate kinases (NDPK) are key enzymes involved in the intracellular nucleotide maintenance in all living organisms, especially in trypanosomatids which are unable to synthesise purines de novo. Four putative NDPK isoforms were identified in the Trypanosoma cruzi Chagas, 1909 genome but only two of them were characterised so far. In this work, we studied a novel isoform from T. cruzi called TcNDPK3. This enzyme presents an atypical N-terminal extension similar to the DM10 domains. In T. cruzi, DM10 sequences targeted other NDPK isoform (TcNDPK2) to the cytoskeleton, but TcNDPK3 was localised in glycosomes despite lacking a typical peroxisomal targeting signal...
February 17, 2017: Folia Parasitologica
https://www.readbyqxmd.com/read/28243589/nuclear-compartmentalization-contributes-to-stage-specific-gene-expression-control-in-trypanosoma-cruzi
#7
Lucía Pastro, Pablo Smircich, Andrés Di Paolo, Lorena Becco, María A Duhagon, José Sotelo-Silveira, Beatriz Garat
In the protozoan parasite Trypanosoma cruzi, as in other trypanosomatids, transcription of protein coding genes occurs in a constitutive fashion, producing large polycistronic transcription units. These units are composed of non-functionally related genes which are pervasively processed to yield each mRNA. Therefore, post-transcriptional processes are crucial to regulate gene expression. Considering that nuclear compartmentalization could contribute to gene expression regulation, we comparatively studied the nuclear, cytoplasmic and whole cell transcriptomes of the non-infective epimastigote stage of T...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28239154/anti-trypanosomatid-drug-discovery-an-ongoing-challenge-and-a-continuing-need
#8
REVIEW
Mark C Field, David Horn, Alan H Fairlamb, Michael A J Ferguson, David W Gray, Kevin D Read, Manu De Rycker, Leah S Torrie, Paul G Wyatt, Susan Wyllie, Ian H Gilbert
The WHO recognizes human African trypanosomiasis, Chagas disease and the leishmaniases as neglected tropical diseases. These diseases are caused by parasitic trypanosomatids and range in severity from mild and self-curing to near invariably fatal. Public health advances have substantially decreased the effect of these diseases in recent decades but alone will not eliminate them. In this Review, we discuss why new drugs against trypanosomatids are required, approaches that are under investigation to develop new drugs and why the drug discovery pipeline remains essentially unfilled...
February 27, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28216511/global-kinetoplastea-phylogeny-inferred-from-a-large-scale-multigene-alignment-including-parasitic-species-for-better-understanding-transitions-from-a-free-living-to-a-parasitic-lifestyle
#9
Euki Yazaki, Sohta A Ishikawa, Keitaro Kume, Akira Kumagai, Takashi Kamaishi, Goro Tanifuji, Tetsuo Hashimoto, Yuji Inagaki
All members of the order Trypanosomatida known to date are parasites that are most likely descendants of a free-living ancestor. Trypanosomatids are an excellent model to assess the transition from a free-living to a parasitic lifestyle, because a large amount of experimental data has been accumulated for well-studied members that are harmful to humans and livestock (Trypanosoma spp. and Leishmania spp.). However, recent advances in our understanding of the diversity of trypanosomatids and their close relatives (i...
February 20, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28213174/evidence-of-the-presence-of-a-calmodulin-sensitive-plasma-membrane-ca-2-atpase-in-trypanosoma-equiperdum
#10
María Carolina Pérez-Gordones, José Rubén Ramírez-Iglesias, Vincenza Cervino, Graciela L Uzcanga, Gustavo Benaim, Marta Mendoza
Trypanosoma equiperdum belongs to the subgenus Trypanozoon, which has a significant socio-economic impact by limiting animal protein productivity worldwide. Proteins involved in the intracellular Ca(2+) regulation are prospective chemotherapeutic targets since several drugs used in experimental treatment against trypanosomatids exert their action through the disruption of the parasite intracellular Ca(2+) homeostasis. Therefore, the plasma membrane Ca(2+)-ATPase (PMCA) is considered as a potential drug target...
February 14, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28212935/dissecting-biochemical-peculiarities-of-the-atpase-activity-of-tcsub2-a-component-of-the-mrna-export-pathway-in-trypanosoma-cruzi
#11
Ize de Aguiar Bittencourt, Mariana Serpeloni, Priscila Mazzochi Hiraiwa, Tatiana de Arruda Campos Brasil de Souza, Andréa Rodrigues Ávila
The RNA helicase DEAD-box protein Sub2 (yeast)/UAP56 (mammals) is conserved across eukaryotes and is essential for mRNA export in trypanosomes. Despite the high conservation of Sub2 in lower eukaryotes such as Trypanosoma cruzi, the low conservation of other mRNA export factors raises questions regarding whether the mode of action of TcSub2 is similar to that of orthologs from other eukaryotes. Mutation of the conserved K87 residue of TcSub2 abolishes ATPase activity, showing that its ATPase domain is functional...
May 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28193733/giant-faz10-is-required-for-flagellum-attachment-zone-stabilization-and-furrow-positioning-in-trypanosoma-brucei
#12
Bernardo Pereira Moreira, Carol Kobori Da Fonseca, Tansy C Hammarton, Munira Muhammad Abdel Baqui
The flagellum and flagellum attachment zone (FAZ) are important cytoskeletal structures in trypanosomatids, being required for motility, cell division and cell morphogenesis. Trypanosomatid cytoskeletons contain abundant high molecular weight proteins (HMWPs), but many of their biological functions are still unclear. Here, we report the characterization of the giant FAZ protein, FAZ10, in Trypanosoma brucei, which we show using immuno-electron microscopy, localises to the intermembrane staples in the FAZ intracellular domain...
February 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28185826/chaetocin-a-histone-methyltransferase-inhibitor-impairs-proliferation-arrests-cell-cycle-and-induces-nucleolar-disassembly-in-trypanosoma-cruzi
#13
Aline Araujo Zuma, Jean de Oliveira Santos, Isabela Mendes, Wanderley de Souza, Carlos Renato Machado, Maria Cristina M Motta
The Trypanosomatidae family includes pathogenic species of medical and veterinary interest. Chagas disease is endemic in Latin America, and about 8 million people are infected worldwide. There is a need for more effective drugs for the acute, undetermined and chronic phases of the disease that, in addition, do not cause side effects, stimulating the search for identification of new drug targets, as well as new chemotherapeutic targets. Trypanosomatids contain characteristic structures, such as the nucleus that undergoes a closed mitosis without chromosome formation and variations of chromatin packing in the different protozoa developmental stages...
February 6, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28185085/h-dependent-inorganic-phosphate-uptake-in-trypanosoma-brucei-is-influenced-by-myo-inositol-transporter
#14
Thais Russo-Abrahão, Carolina Macedo Koeller, Michael E Steinmann, Stephanie Silva-Rito, Thaissa Marins-Lucena, Michele Alves-Bezerra, Naira Ligia Lima-Giarola, Iron Francisco de-Paula, Amaia Gonzalez-Salgado, Erwin Sigel, Peter Bütikofer, Katia Calp Gondim, Norton Heise, José Roberto Meyer-Fernandes
Trypanosoma brucei is an extracellular protozoan parasite that causes human African trypanosomiasis or "sleeping sickness". During the different phases of its life cycle, T. brucei depends on exogenous inorganic phosphate (Pi), but little is known about the transport of Pi in this organism. In the present study, we showed that the transport of (32)Pi across the plasma membrane follows Michaelis-Menten kinetics and is modulated by pH variation, with higher activity at acidic pH. Bloodstream forms presented lower Pi transport in comparison to procyclic forms, that displayed an apparent K0...
February 9, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28167207/ornithine-decarboxylase-or-gamma-glutamylcysteine-synthetase-overexpression-protects-leishmania-vianna-guyanensis-against-antimony
#15
Maisa S Fonseca, Marcelo A Comini, Bethânia V Resende, Ana Maria M Santi, Antônio P Zoboli, Douglas S Moreira, Silvane M F Murta
Trypanosomatids present a unique mechanism for detoxification of peroxides that is dependent on trypanothione (bisglutathionylspermidine). Ornithine decarboxylase (ODC) and γ-glutamylcysteine synthetase (GSH1) produce molecules that are direct precursors of trypanothione. In this study, Leishmania guyanensis odc and gsh1 overexpressor cell lines were generated to investigate the contribution of these genes to the trivalent antimony (Sb(III))-resistance phenotype. The ODC- or GSH1-overexpressors parasites presented an increase of two and four-fold in Sb(III)-resistance index, respectively, when compared with the wild-type line...
February 3, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28161835/changes-in-lipid-and-fatty-acid-composition-during-intramacrophagic-transformation-of-leishmania-donovani-complex-promastigotes-into-amastigotes
#16
Hana Bouazizi-Ben Messaoud, Marion Guichard, Philippe Lawton, Isabelle Delton, Samira Azzouz-Maache
Leishmania sp., are trypanosomatid parasites that are phagocytized by human and animal macrophages. Transformation from the vector promastigote stage to the intracellular amastigote host cell stage is mandatory, since development in the host depends on the internalization of the parasite. We identified and analyzed the lipids involved in the promastigote to amastigote transformation process in the Leishmania donovani complex. Four lipid classes, phospholipids, free fatty acids, triglycerides and sterols were studied...
February 4, 2017: Lipids
https://www.readbyqxmd.com/read/28158179/trypsnetdb-an-integrated-framework-for-the-functional-characterization-of-trypanosomatid-proteins
#17
Vahid H Gazestani, Chun Wai Yip, Najmeh Nikpour, Natasha Berghuis, Reza Salavati
Trypanosomatid parasites cause serious infections in humans and production losses in livestock. Due to the high divergence from other eukaryotes, such as humans and model organisms, the functional roles of many trypanosomatid proteins cannot be predicted by homology-based methods, rendering a significant portion of their proteins as uncharacterized. Recent technological advances have led to the availability of multiple systematic and genome-wide datasets on trypanosomatid parasites that are informative regarding the biological role(s) of their proteins...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28135300/comprehensive-identification-of-mrna-binding-proteins-of-leishmania-donovani-by-interactome-capture
#18
Devki Nandan, Sneha A Thomas, Anne Nguyen, Kyung-Mee Moon, Leonard J Foster, Neil E Reiner
Leishmania are unicellular eukaryotes responsible for leishmaniasis in humans. Like other trypanosomatids, leishmania regulate protein coding gene expression almost exclusively at the post-transcriptional level with the help of RNA binding proteins (RBPs). Due to the presence of polycystronic transcription units, leishmania do not regulate RNA polymerase II-dependent transcription initiation. Recent evidence suggests that the main control points in gene expression are mRNA degradation and translation. Protein-RNA interactions are involved in every aspect of RNA biology, such as mRNA splicing, polyadenylation, localization, degradation, and translation...
2017: PloS One
https://www.readbyqxmd.com/read/28081121/isolation-of-novel-trypanosomatid-zelonia-australiensis-sp-nov-kinetoplastida-trypanosomatidae-provides-support-for-a-gondwanan-origin-of-dixenous-parasitism-in-the-leishmaniinae
#19
Joel Barratt, Alexa Kaufer, Bryce Peters, Douglas Craig, Andrea Lawrence, Tamalee Roberts, Rogan Lee, Gary McAuliffe, Damien Stark, John Ellis
The genus Leishmania includes approximately 53 species, 20 of which cause human leishmaniais; a significant albeit neglected tropical disease. Leishmaniasis has afflicted humans for millennia, but how ancient is Leishmania and where did it arise? These questions have been hotly debated for decades and several theories have been proposed. One theory suggests Leishmania originated in the Palearctic, and dispersed to the New World via the Bering land bridge. Others propose that Leishmania evolved in the Neotropics...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28076955/post-translational-modifications-of-trypanosoma-cruzi-canonical-and-variant-histones
#20
Gisele F A Picchi, Vanessa Zulkievicz, Marco A Krieger, Nilson T Zanchin, Samuel Goldenberg, Lyris M F de Godoy
Chagas disease, caused by Trypanosoma cruzi, still affects millions of people around the world. No vaccines nor treatment for chronic Chagas disease are available, and chemotherapy for the acute phase is hindered by limited efficacy and severe side effects. The processes by which the parasite acquires infectivity and survives in different hosts involve tight regulation of gene expression, mainly post-transcriptionally. Nevertheless, chromatin structure/organization of trypanosomatids is similar to other eukaryotes, including histone variants and post-translational modifications...
January 30, 2017: Journal of Proteome Research
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