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Trypanosomatids

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https://www.readbyqxmd.com/read/28426655/glycosome-biogenesis-in-trypanosomes-and-the-de-novo-dilemma
#1
REVIEW
Sarah Bauer, Meredith T Morris
Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28414928/new-iminodibenzyl-derivatives-with-anti-leishmanial-activity
#2
Anderson Arndt, Cleber Wanderlei Liria, Jenicer K U Yokoyama-Yasunaka, M Terêsa Machini, Sílvia Reni Bortolin Uliana, Breno Pannia Espósito
Leishmaniasis is an infection caused by protozoa of the genus Leishmania and transmitted by sandflies. Current treatments are expensive and time-consuming, involving Sb(V)-based compounds, lipossomal amphotericin B and miltefosine. Recent studies suggest that inhibition of trypanothione reductase (TR) could be a specific target in the development of new drugs because it is essential and exclusive to trypanosomatids. This work presents the synthesis and characterization of new iminodibenzyl derivatives (dado) with ethylenediamine (ea), ethanolamine (en) and diethylenetriamine (dien) and their copper(II) complexes...
April 4, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28406895/the-superfamily-keeps-growing-identification-in-trypanosomatids-of-ribj-the-first-riboflavin-transporter-family-in-protists
#3
Darío E Balcazar, María Cristina Vanrell, Patricia S Romano, Claudio A Pereira, Fernando A Goldbaum, Hernán R Bonomi, Carolina Carrillo
BACKGROUND: Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors...
April 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28397756/anti-trypanosomatid-elemanolide-sesquiterpene-lactones-from-vernonia-lasiopus-o-hoffm
#4
Njogu M Kimani, Josphat C Matasyoh, Marcel Kaiser, Reto Brun, Thomas J Schmidt
Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples' lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid "protozoan" parasite Trypanosoma brucei. The parasites are transmitted to humans through bites of infected tsetse flies of the genus Glossina. The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection...
April 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28388690/a-leucine-aminopeptidase-is-involved-in-kinetoplast-dna-segregation-in-trypanosoma-brucei
#5
Priscila Peña-Diaz, Marie Vancová, Christian Resl, Mark C Field, Julius Lukeš
The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication mechanism remain uncharacterized at the molecular level, one of which is the nabelschnur or umbilicus, a prominent structure which in the mammalian parasite Trypanosoma brucei connects the daughter kDNA networks prior to their segregation...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28386020/evolution-of-the-endomembrane-systems-of-trypanosomatids-conservation-and-specialisation
#6
Divya Venkatesh, Cordula Boehm, Lael D Barlow, Nerissa N Nankissoor, Amanda O'Reilly, Steven Kelly, Joel B Dacks, Mark C Field
Parasite surfaces support multiple functions required for survival within their hosts, and maintenance and functionality of the surface depends on membrane trafficking. To understand the evolutionary history of trypanosomatid trafficking, where multiple lifestyles and mechanisms of host interactions are known, we examined protein families central to defining intracellular compartments and mediating transport, namely Rabs, SNAREs and RabGAPs, across all available Euglenozoa genomes. Bodonids possess a large trafficking repertoire, which is mainly retained by the Trypanosoma cruzi group, with extensive losses in other lineages, particularly African trypanosomes and phytomonads...
April 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28385563/evidence-of-putative-non-coding-rnas-from-leishmania-untranslated-regions
#7
Felipe Freitas Castro, Patricia C Ruy, Karina Nogueira Zeviani, Ramon Freitas Santos, Juliano Simões Toledo, Angela Kaysel Cruz
Non-coding RNAs (ncRNAs) are regulatory elements present in a wide range of organisms, including trypanosomatids. ncRNAs transcribed from the untranslated regions (UTRs) of coding genes have been described in the transcriptomes of several eukaryotes, including Trypanosoma brucei. To uncover novel putative ncRNAs in two Leishmania species, we examined a L. major cDNA library and a L. donovani non-polysomal RNA library. Using a combination of computational analysis and experimental approaches, we classified 26 putative ncRNA in L...
April 3, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28371652/the-symbiotic-bacterium-fuels-the-energy-metabolism-of-the-host-trypanosomatid-strigomonas-culicis
#8
Ana Carolina Loyola-Machado, Allan Cézar Azevedo-Martins, Carolina Moura Costa Catta-Preta, Wanderley de Souza, Antonio Galina, Maria Cristina M Motta
The mutualistic relationship between trypanosomatids and their respective endosymbiotic bacteria represents an excellent model for studying metabolic co-evolution since the symbiont completes essential biosynthetic routes of the host cell. In this work, we investigated the influence of the endosymbiont on the energy metabolism of Strigomonas culicis by comparing the wild strain with aposymbiotic protists. The bacterium maintains a frequent and close association with glycosomes, which are distributed around the prokaryote...
February 28, 2017: Protist
https://www.readbyqxmd.com/read/28367781/simple-dialkyl-pyrazole-3-5-dicarboxylates-show-in-vitro-and-in-vivo-activity-against-disease-causing-trypanosomatids
#9
Felipe Reviriego, Francisco Olmo, Pilar Navarro, Clotilde Marín, Inmaculada Ramírez-Macías, Enrique García-España, María Teresa Albelda, Ramón Gutiérrez-Sánchez, Manuel Sánchez-Moreno, Vicente J Arán
The synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2-6) and their sodium salts (pyrazolates) (compounds 7-9) against Trypanosoma cruzi, Leishmania infantum and Leishmania braziliensis are reported. In most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for T. cruzi and glucantime for Leishmania spp.); furthermore, the low non-specific cytotoxicities against Vero cells and macrophages shown by these compounds led to good selectivity indexes, which are 8-72 times higher for T...
April 3, 2017: Parasitology
https://www.readbyqxmd.com/read/28358927/aquaglyceroporin-null-trypanosomes-display-glycerol-transport-defects-and-respiratory-inhibitor-sensitivity
#10
Laura Jeacock, Nicola Baker, Natalie Wiedemar, Pascal Mäser, David Horn
Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28357394/a-multigene-family-encoding-surface-glycoproteins-in-trypanosoma-congolense
#11
Magali Thonnus, Amandine Guérin, Loïc Rivière
Trypanosoma congolense, the causative agent of the most important livestock disease in Africa, expresses specific surface proteins involved in its parasitic lifestyle. Unfortunately, the complete repertoire of such molecules is far from being deciphered. As these membrane components are exposed to the host environment, they could be used as therapeutic or diagnostic targets. By mining the T. congolense genome database, we identified a novel family of lectin-like glycoproteins (TcoClecs). These molecules are predicted to have a transmembrane domain, a tandem repeat amino acid motif, a signal peptide and a C-type lectin-like domain (CTLD)...
March 2, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28347500/versatility-of-peroxisomes-an-evolving-concept
#12
REVIEW
Rachayeeta Deb, Shirisha Nagotu
Research spanning almost 50 years has highlighted unique characteristics and irreplaceable list of diverse functions performed by peroxisomes in various model systems. Peroxisomes are single membrane bound highly dynamic organelles ubiquitous to most eukaryotic cells. Proliferation by division of pre-existing organelles and the role of endoplasmic reticulum in the biogenesis of these organelles is now well established. The earliest identified conserved functions of peroxisomes are β-oxidation of fatty acids and reactive oxygen species metabolism...
April 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28338335/stress-induced-protein-s-glutathionylation-and-s-trypanothionylation-in-african-trypanosomes-a-quantitative-redox-proteome-and-thiol-analysis
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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