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Céline Ronin, David Mendes Costa, Joana Tavares, Joana Faria, Fabrice Ciesielski, Paola Ciapetti, Terry K Smith, Jane MacDougall, Anabela Cordeiro-da-Silva, Iain K Pemberton
The de novo crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1 (LiSir2rp1) has been solved at 1.99Å in complex with an acetyl-lysine peptide substrate. The structure is broadly commensurate with Hst2/SIRT2 proteins of yeast and human origin, reproducing many of the structural features common to these sirtuin deacetylases, including the characteristic small zinc-binding domain, and the larger Rossmann-fold domain involved in NAD+-binding interactions. The two domains are linked via a cofactor binding loop ordered in open conformation...
2018: PloS One
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
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
Noel-Marie Plonski, Bianca Bissoni, Madara Hetti Arachchilage, Karl Romstedt, Edgar E Kooijman, Helen Piontkivska
Unicellular flagellates that make up the class Kinetoplastida include multiple parasites responsible for public health concerns, including Trypanosoma brucei and T. cruzi (agents of African sleeping sickness and Chagas disease, respectively), and various Leishmania species, which cause leishmaniasis. These diseases are generally difficult to eradicate, with treatments often having lethal side effects and/or being effective only during the acute phase of the diseases, when most patients are still asymptomatic...
February 28, 2018: Gene
Catarina A Marques, Richard McCulloch
Introduction: Understanding how the nuclear genome of kinetoplastid parasites is replicated received experimental stimulus from sequencing of the Leishmania major, Trypanosoma brucei and Trypanosoma cruzi genomes around 10 years ago. Gene annotations suggested key players in DNA replication initiation could not be found in these organisms, despite considerable conservation amongst characterised eukaryotes. Initial studies that indicated trypanosomatids might possess an archaeal-like Origin Recognition Complex (ORC), composed of only a single factor termed ORC1/CDC6, have been supplanted by the more recent identification of an ORC in T...
February 2018: Current Genomics
João Luís Reis-Cunha, Hugo O Valdivia, Daniella Castanheira Bartholomeu
Trypanosomatids are a group of kinetoplastid parasites including some of great public health importance, causing debilitating and life-long lasting diseases that affect more than 24 million people worldwide. Among the trypanosomatids, Trypanosoma cruzi, Trypanosoma brucei and species from the Leishmania genus are the most well studied parasites, due to their high prevalence in human infections. These parasites have an extreme genomic and phenotypic variability, with a massive expansion in the copy number of species-specific multigene families enrolled in host-parasite interactions that mediate cellular invasion and immune evasion processes...
February 2018: Current Genomics
Esteban D Erben
From synthesis to decay, mRNA associates with RNA-binding proteins (RBPs) establishing dynamic ribonucleoprotein particles (RNPs). Understanding the composition and function of RNPs is fundamental to understanding how eukaryotic mRNAs are controlled. This is especially relevant for trypanosomes and related kinetoplastid parasites, which mostly rely on post-transcriptional mechanisms to control gene expression. Crucial for trypanosome differentiation, development, or even response to heat shock, RBPs are known to be essential modulators of diverse molecular processes...
February 2018: Current Genomics
Luis Miguel De Pablos
No abstract text is available yet for this article.
February 2018: Current Genomics
Alejandro G Schijman
Chagas disease, caused by the kinetoplastid protozoan Trypanosoma cruzi, affects millions of people, most of them neglected populations. The different phases of the disease, the transmission mode and the high genetic variability of the parasite determine that molecular detection methods display different degree of success. Molecular diagnostic tests may be employed during epidemiological surveys of transmission, for early diagnosis of congenital transmission and acute infections due to oral transmission, transfusion or transplantation routes, reactivation due to immunosuppression and monitoring of treatment response in chronically infected patients receiving trypanocidal chemotherapy...
February 21, 2018: Acta Tropica
Julius Mulindwa, Kevin Leiss, David Ibberson, Kevin Kamanyi Marucha, Claudia Helbig, Larissa Melo do Nascimento, Eleanor Silvester, Keith Matthews, Enock Matovu, John Enyaru, Christine Clayton
All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of human patients with those of trypanosomes from culture and rodents. The data were aligned and analysed using new user-friendly applications designed for Kinetoplastid RNA-Seq data. The transcriptomes of trypanosomes from human blood and cerebrospinal fluid did not predict major metabolic differences that might affect drug susceptibility...
February 23, 2018: PLoS Neglected Tropical Diseases
R Tyler Weisbarth, Anish Das, Paul Castellano, Michael A Fisher, Han Wu, Vivian Bellofatto
Trypanosoma cruzi, the protozoan parasite that causes Chagas disease in humans, has a complex life cycle that promotes survival in disparate environments. In each environment, the parasite must fine-tune its metabolic pathways to divide and multiply. In the absence of recognizable transcriptional gene regulation, it is apparent that protein levels are determined by post-transcriptional mechanisms. Post-transcriptional gene control is influenced by RNA-binding proteins that target mRNAs in the cell's cytoplasm...
February 23, 2018: Parasitology Research
Neeloo Singh, Renu Goel, Ekta Jain
PURPOSE: Although in trypanosomatids, monoxeny (Leptomonas) is ancestral to dixeny (Leishmania), however clinical cases of visceral leishmanisis with Leptomonas co-infection are increasingly being reported from India. Using a proteogenomic approach, we carried out a detailed proteome analysis of these two kinetoplastid parasites viz. Leishmania and its sister Leptomonas, to catalog the key proteins associated with and therefore possibly responsible for phenotype changes in Leptomonas evolution and domestication as co-infection with Leishmania...
February 22, 2018: Proteomics. Clinical Applications
Ning Zhang, Martin Zoltner, Ka-Fai Leung, Paul Scullion, Sebastian Hutchinson, Ricardo C Del Pino, Isabel M Vincent, Yong-Kang Zhang, Yvonne R Freund, Michael R K Alley, Robert T Jacobs, Kevin D Read, Michael P Barrett, David Horn, Mark C Field
Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in Trypanosoma brucei...
February 9, 2018: PLoS Pathogens
Jason Carnes, Suzanne M McDermott, Kenneth Stuart
Editosomes are the multiprotein complexes that catalyze the insertion and deletion of uridines to create translatable mRNAs in the mitochondria of kinetoplastids. Recognition and cleavage of a broad diversity of RNA substrates in vivo require three functionally distinct RNase III-type endonucleases, as well as five additional editosome proteins that contain noncatalytic RNase III domains. RNase III domains have recently been identified in the editosome accessory proteins KREPB9 and KREPB10, suggesting a role related to editing endonuclease function...
January 2018: MSphere
Denise Andréa Silva de Souza, Daniela Parada Pavoni, Marco Aurélio Krieger, Adriana Ludwig
Myosins are motor proteins that comprise a large and diversified family important for a broad range of functions. Two myosin classes, I and XIII, were previously assigned in Trypanosomatids, based mainly on the studies of Trypanosoma cruzi, T. brucei and Leishmania major, and important human pathogenic species; seven orphan myosins were identified in T. cruzi. Our results show that the great variety of T. cruzi myosins is also present in some closely related species and in Bodo saltans, a member of an early divergent branch of Kinetoplastida...
January 22, 2018: Scientific Reports
Pedro S Pereira, Ana J Maia, Antônia E Duarte, Cícera Datiane M Oliveira-Tintino, Saulo R Tintino, Luiz M Barros, Maria C Vega-Gomez, Miriam Rolón, Cathia Coronel, Henrique D M Coutinho, Teresinha G da Silva
AlpiniA speciosa K. Schum, known as colônia (colony), is native to tropical Asia and found in parts of tropical America. Its leaves are used to wrap food, rhizomes for food preparation and seeds for health maintenance, and have been widely used by the population as a diuretic, antihypertensive, antiulcerogenic and sedative. The present study aimed to verify the leishmanicidal and trypanocidal potential, as well as the cytotoxicity, of the A. speciosa essential oil, in vitro. A. speciosa presented 1,8-cineole (28...
January 17, 2018: Food and Chemical Toxicology
Armando Jardim, Darryl B Hardie, Jan Boitz, Christoph H Borchers
To facilitate a greater understanding of the biological processes in the medically important Leishmania donovani parasite, a combination of differential and density-gradient ultracentrifugation techniques were used to achieve a comprehensive subcellular fractionation of the promastigote stage. An in-depth label-free proteomic LC-MS/MS analysis of the density gradients resulted in the identification of ~50% of the Leishmania proteome (3883 proteins detected), which included ~645 integral membrane proteins and 1737 uncharacterized proteins...
January 15, 2018: Journal of Proteome Research
Binnypreet Kaur, Matus Valach, Priscila Peña-Diaz, Sandrine Moreira, Patrick J Keeling, Gertraud Burger, Julius Lukeš, Drahomíra Faktorová
Diplonema papillatum is the type species of diplonemids, which are among the most abundant and diverse heterotrophic micro-eukaryotes in the world's oceans. Diplonemids are also known for a unique form of post-transcriptional processing in mitochondria. However, the lack of reverse genetics methodologies in these protists has hampered elucidation of their cell and molecular biology. Here we report a protocol for D. papillatum transformation. We have identified several antibiotics to which D. papillatum is sensitive and thus are suitable selectable markers, and focus in particular on puromycin...
January 10, 2018: Environmental Microbiology
Sandra Specht, Linda Liedgens, Margarida Duarte, Alexandra Stiegler, Ulrike Wirth, Maike Eberhardt, Ana Tomás, Kai Hell, Marcel Deponte
Mia40/CHCHD4 and Erv1/ALR are essential for oxidative protein folding in the mitochondrial intermembrane space of yeast and mammals. In contrast, many protists, including important apicomplexan and kinetoplastid parasites, lack Mia40. Furthermore, the Erv homolog of the model parasite Leishmania tarentolae (LtErv) was shown to be incompatible with Saccharomyces cerevisiae Mia40 (ScMia40). Here we addressed structure-function relationships of ScErv1 and LtErv as well as their compatibility with the oxidative protein folding system in yeast using chimeric, truncated, and mutant Erv constructs...
December 23, 2017: Redox Biology
Paul Schmid-Hempel, Markus Aebi, Seth Barribeau, Toshihiko Kitajima, Louis du Plessis, Regula Schmid-Hempel, Stefan Zoller
Trypanosomatids (Trypanosomatidae, Kinetoplastida) are flagellated protozoa containing many parasites of medical or agricultural importance. Among those, Crithidia bombi and C. expoeki, are common parasites in bumble bees around the world, and phylogenetically close to Leishmania and Leptomonas. They have a simple and direct life cycle with one host, and partially castrate the founding queens greatly reducing their fitness. Here, we report the nuclear genome sequences of one clone of each species, extracted from a field-collected infection...
2018: PloS One
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