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Trypanosomatids

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https://www.readbyqxmd.com/read/29339220/a-new-chimeric-triple-reporter-fusion-protein-as-a-tool-for-in-vitro-and-in-vivo-multimodal-imaging-to-monitor-the-development-of-african-trypanosomes-and-leishmania-parasites
#1
Estefania Calvo Alvarez, Christelle Cren-Travaillé, Aline Crouzols, Brice Rotureau
Trypanosomiases and leishmaniases, caused by a group of related protist parasites, are Neglected Tropical Diseases currently threatening >500 million people worldwide. Reporter proteins have revolutionised the research on infectious diseases and have opened up new advances in the understanding of trypanosomatid-borne diseases in terms of both biology, pathogenesis and drug development. Here, we describe the generation and some applications of a new chimeric triple reporter fusion protein combining the red-shifted firefly luciferase PpyREH9 and the tdTomato red fluorescent protein, fused by the TY1 tag...
January 12, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29313667/design-and-synthesis-of-broad-spectrum-trypanosomatid-selective-inhibitors
#2
Andrew L Fraser, Stefanie K Menzies, Elizabeth F B King, Lindsay B Tulloch, Eoin R Gould, Marija Zacharova, Terry K Smith, Gordon J Florence
Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern that have a devastating effect on the developing world due to their burden on human and animal health. In this work, we detail the preparation of a focused library of substituted-tetrahydropyran derivatives and their evaluation as selective chemical tools for trypanosomatid inhibition and the follow-on development of photo-affinity probes capable of labeling target protein(s) in vitro. Several of these functionalised compounds maintain low micromolar activity against Trypanosoma brucei, Trypanosoma cruzi, Leishmania major and Leishmania donovani...
January 9, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29304093/the-genomes-of-crithidia-bombi-and-c-expoeki-common-parasites-of-bumblebees
#3
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
https://www.readbyqxmd.com/read/29288414/trypanosoma-brucei-eif4e2-cap-binding-protein-binds-a-homolog-of-the-histone-mrna-stem-loop-binding-protein
#4
Eden R Freire, Danielle M N Moura, Maria J R Bezerra, Camila C Xavier, Mariana C Morais-Sobral, Ajay A Vashisht, Antonio M Rezende, James A Wohlschlegel, Nancy R Sturm, Osvaldo P de Melo Neto, David A Campbell
Trypanosomatids are parasitic protozoans characterized by several unique structural and metabolic processes that include exquisite mechanisms associated with gene expression and regulation. During the initiation of protein synthesis, for instance, mRNA selection for translation seems to be mediated by different eIF4F-like complexes, which may play a significant role in parasite adaptation to different hosts. In eukaryotes, the heterotrimeric eIF4F complex (formed by eIF4E, eIF4G, and eIF4A) mediates mRNA recognition and ribosome binding and participates in various translation regulatory events...
December 29, 2017: Current Genetics
https://www.readbyqxmd.com/read/29286188/the-mitochondrial-calcium-uniporter-complex-in-trypanosomes
#5
REVIEW
Noelia Lander, Miguel A Chiurillo, Mayara S Bertolini, Roberto Docampo, Aníbal E Vercesi
The presence of a conserved mechanism for mitochondrial calcium uptake in trypanosomatids was crucial for the molecular identification of the mitochondrial calcium uniporter (MCU), a long-sought channel present in most eukaryotic organisms. Since then, research efforts to elucidate the role of MCU and its regulatory elements in different biological models have multiplied. MCU is the pore-forming subunit of a multimeric complex (the MCU complex or MCUC) and its predicted structure in trypanosomes is simpler than in mammalian cells, lacking two of its subunits and probably possessing other unidentified components...
December 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29284754/viral-discovery-and-diversity-in-trypanosomatid-protozoa-with-a-focus-on-relatives-of-the-human-parasite-leishmania
#6
Danyil Grybchuk, Natalia S Akopyants, Alexei Y Kostygov, Aleksandras Konovalovas, Lon-Fye Lye, Deborah E Dobson, Haroun Zangger, Nicolas Fasel, Anzhelika Butenko, Alexander O Frolov, Jan Votýpka, Claudia M d'Avila-Levy, Pavel Kulich, Jana Moravcová, Pavel Plevka, Igor B Rogozin, Saulius Serva, Julius Lukeš, Stephen M Beverley, Vyacheslav Yurchenko
Knowledge of viral diversity is expanding greatly, but many lineages remain underexplored. We surveyed RNA viruses in 52 cultured monoxenous relatives of the human parasite Leishmania (Crithidia and Leptomonas), as well as plant-infecting PhytomonasLeptomonas pyrrhocoris was a hotbed for viral discovery, carrying a virus (Leptomonas pyrrhocoris ostravirus 1) with a highly divergent RNA-dependent RNA polymerase missed by conventional BLAST searches, an emergent clade of tombus-like viruses, and an example of viral endogenization...
December 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29282526/triplex-real-time-pcr-for-detection-of-crithidia-mellificae-and-lotmaria-passim-in-honey-bees
#7
Guang Xu, Evan Palmer-Young, Kim Skyrm, Timothy Daly, Martha Sylvia, Anne Averill, Stephen Rich
Currently, light microscopic examination of cell morphology cannot discriminate Crithidia mellificae and Lotmaria passim with 100% certainty. Here, a minor groove-binding (MGB) probe-based multiplex real-time PCR assay was developed for the simultaneous and quantitative detection of C. mellificae and L. passim in honey bees. A conserved Hymenoptera 18S rRNA gene was built in as an internal control that allows accurate detection of PCR inhibition and failure of DNA extraction. The newly developed assay was also applied to field samples...
December 27, 2017: Parasitology Research
https://www.readbyqxmd.com/read/29258569/leishmania-braziliensis-scd6-and-rbp42-proteins-two-factors-with-rna-binding-capacity
#8
Paola A Nocua, Cesar A Ramirez, José M Requena, Concepción J Puerta
BACKGROUND: The study of RNA binding proteins (RBPs) is of great relevance for understanding processes like post-transcriptional control of gene expression. The post-transcriptional mechanisms are particularly important in Leishmania parasites and related trypanosomatids since transcriptional regulation is almost absent in them. Thus, RBPs should be essential during the development of these parasites and for survival strategies against the adverse conditions that they face during their life-cycle...
December 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29248681/characteristics-and-application-of-s1-p1-nucleases-in-biotechnology-and-medicine
#9
REVIEW
Tomáš Kovaľ, Jan Dohnálek
3'-nucleases/nucleotidases of the S1-P1 family (EC 3.1.30.1) are single-strand-specific or non-specific zinc-dependent phosphoesterases present in plants, fungi, protozoan parasites, and in some bacteria. They participate in a wide variety of biological processes and their current biotechnological applications rely on their single-strand preference, nucleotide non-specificity, a broad range of catalytic conditions and high stability. We summarize the present and potential utilization of these enzymes in biotechnology and medicine in the context of their biochemical and structure-function properties...
December 14, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/29246805/substrate-specificity-profiling-of-m32-metallocarboxypeptidases-from-trypanosoma-cruzi-and-trypanosoma-brucei
#10
Alejandra P Frasch, León A Bouvier, Florencia M Oppenheimer, Maria Aparecida Juliano, Luiz Juliano, Adriana K Carmona, Juan José Cazzulo, Gabriela T Niemirowicz
Metallocarboxypeptidases (MCPs) of the M32 family, while broadly distributed among prokaryotic organisms, have so far been only found in a few eukaryotes including trypanosomatids. Among these organisms are human and animal pathogens of medical relevance such as Trypanosoma brucei and Trypanosoma cruzi, the respective causative agents of sleeping sickness and Chagas disease. The M32 MCP orthologues found in these parasites share 72% protein sequence identity. They also present a cytosolic localization, a similar pattern of expression and a marked preference for Arg/Lys residues at P1'...
December 12, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29220521/trypanosomatid-mitochondrial-rna-editing-dramatically-complex-transcript-repertoires-revealed-with-a-dedicated-mapping-tool
#11
Evgeny S Gerasimov, Anna A Gasparyan, Iosif Kaurov, Boris Tichý, Maria D Logacheva, Alexander A Kolesnikov, Julius Lukeš, Vyacheslav Yurchenko, Sara L Zimmer, Pavel Flegontov
RNA editing by targeted insertion and deletion of uridine is crucial to generate translatable mRNAs from the cryptogenes of the mitochondrial genome of kinetoplastids. This type of editing consists of a stepwise cascade of reactions generally proceeding from 3' to 5' on a transcript, resulting in a population of partially edited as well as pre-edited and completely edited molecules for each mitochondrial cryptogene of these protozoans. Often, the number of uridines inserted and deleted exceed the number of nucleotides that are genome-encoded...
December 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29211037/in-silico-identification-and-in-vitro-evaluation-of-natural-inhibitors-of-leishmania-major-pteridine-reductase-i
#12
Fabian C Herrmann, Nirina Sivakumar, Joachim Jose, Maria P Costi, Cecilia Pozzi, Thomas J Schmidt
In a continuation of our computational efforts to find new natural inhibitors of a variety of target enzymes from parasites causing neglected tropical diseases (NTDs), we now report on 15 natural products (NPs) that we have identified as inhibitors of Leishmania major pteridine reductase I (LmPTR1) through a combination of in silico and in vitro investigations. Pteridine reductase (PTR1) is an enzyme of the trypanosomatid parasites' peculiar folate metabolism, and has previously been validated as a drug target...
December 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29210635/potential-drug-targets-in-the-pentose-phosphate-pathway-of-trypanosomatids
#13
Ines Loureiro, Joana Faria, Nuno Santarem, Terry K Smith, Joana Tavares, Anabela Cordeiro-da-Silva
The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such African sleeping sickness, Chagas' disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, important in the maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose 5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic amino acids, are produced...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29159213/dataset-generated-for-dissection-of-mechanisms-of-trypanothione-reductase-and-tryparedoxin-peroxidase-through-dynamic-network-analysis-and-simulations-in-leishmaniasis
#14
Anurag Kumar, Bhaskar Saha, Shailza Singh
Leishmaniasis is the second largest parasitic killer disease caused by the protozoan parasite Leishmania, transmitted by the bite of sand flies. It's endemic in the eastern India with 165.4 million populations at risk with the current drug regimen. Three forms of leishmaniasis exist in which cutaneous is the most common form caused by Leishmania major. Trypanothione Reductase (TryR), a flavoprotein oxidoreductase, unique to thiol redox system, is considered as a potential target for chemotherapy for trypanosomatids infection...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29140234/prevalence-of-trypanosoma-cruzi-and-other-trypanosomatids-in-frequently-hunted-wild-mammals-from-the-peruvian-amazon
#15
E Angelo Morales, Pedro Mayor, Mark Bowler, Esar Aysanoa, Erika S Pérez-Velez, Jocelyn Pérez, Julio A Ventocilla, G Christian Baldeviano, Andrés G Lescano
To better understand the ecology of Trypanosoma cruzi in the northeastern Peruvian Amazon, we evaluated the prevalence of T. cruzi and other trypanosomatids in four orders of wild mammals hunted and consumed by inhabitants of three remote indigenous communities in the Peruvian Amazon. Of 300 wild mammals sampled, 115 (38.3%) were infected with trypanosomatids and 15 (5.0%) with T. cruzi. The prevalence of T. cruzi within each species was as follows: large rodents (Cuniculus paca, 5.5%; Dasyprocta spp., 2.6%), edentates (Dasypus novemcinctus, 4...
November 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29131838/expanded-repertoire-of-kinetoplast-associated-proteins-and-unique-mitochondrial-dna-arrangement-of-symbiont-bearing-trypanosomatids
#16
Silvana Sant Anna de Souza, Carolina Moura Catta-Preta, João Marcelo P Alves, Danielle P Cavalcanti, Marta M G Teixeira, Erney P Camargo, Wanderley De Souza, Rosane Silva, Maria Cristina M Motta
In trypanosomatids, the kinetoplast is the portion of the single mitochondrion that is connected to the basal body and contains the kDNA, a network composed by circular and interlocked DNA. The kDNA packing is conducted by Kinetoplast Associated Proteins (KAPs), which are similar to eukaryotic histone H1. In symbiont-harboring trypanosomatids (SHTs) such as Angomonas deanei and Strigomonas culicis, a ß-proteobacterium co-evolves with the host in a mutualistic relationship. The prokaryote confers nutritional benefits to the host and affects its cell structure...
2017: PloS One
https://www.readbyqxmd.com/read/29121981/intrinsic-dna-curvature-in-trypanosomes
#17
Pablo Smircich, Najib M El-Sayed, Beatriz Garat
BACKGROUND: Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed...
November 9, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29114029/rapid-selection-free-high-efficiency-genome-editing-in-protozoan-parasites-using-crispr-cas9-ribonucleoproteins
#18
Lia Carolina Soares Medeiros, Lilith South, Duo Peng, Juan M Bustamante, Wei Wang, Molly Bunkofske, Natasha Perumal, Fernando Sanchez-Valdez, Rick L Tarleton
Trypanosomatids (order Kinetoplastida), including the human pathogens Trypanosoma cruzi (agent of Chagas disease), Trypanosoma brucei, (African sleeping sickness), and Leishmania (leishmaniasis), affect millions of people and animals globally. T. cruzi is considered one of the least studied and most poorly understood tropical disease-causing parasites, in part because of the relative lack of facile genetic engineering tools. This situation has improved recently through the application of clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) technology, but a number of limitations remain, including the toxicity of continuous Cas9 expression and the long drug marker selection times...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29113738/quantitative-pcr-assessment-of-lotmaria-passim-in-apis-mellifera-colonies-co-infected-naturally-with-nosema-ceranae
#19
Branislav Vejnovic, Jevrosima Stevanovic, Ryan S Schwarz, Nevenka Aleksic, Milorad Mirilovic, Nemanja M Jovanovic, Zoran Stanimirovic
A recently described trypanosomatid species Lotmaria passim and the microsporidium Nosema ceranae infect the honey bee (Apis mellifera), but the interspecific dynamic of these two common gut parasites is unknown. In this study, a real-time qPCR assay was developed to enable the specific detection and quantification of L. passim. The annual dynamics of N. ceranae and L. passim infections were evaluated in ten A. mellifera colonies naturally infected with both parasites at one apiary in Serbia from March 2016 to March 2017...
November 4, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29107734/involvement-of-snare-protein-ykt6-in-glycosome-biogenesis-in-trypanosoma-brucei
#20
Hiren Banerjee, Richard A Rachubinski
The kinetoplastid parasites Trypanosoma and Leishmania are etiologic agents of diseases like African sleeping sickness, Chagas and leishmaniasis that inflict many tropical and subtropical parts of the world. These parasites are distinctive in that they compartmentalize most of the usually cytosolic enzymes of the glycolytic pathway within a peroxisome-like organelle called the glycosome. Functional glycosomes are essential in both the procyclic and bloodstream forms of trypanosomatid parasites, and mislocalization of glycosomal enzymes to the cytosol is fatal for the parasite...
December 2017: Molecular and Biochemical Parasitology
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