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Kinetoplastids

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https://www.readbyqxmd.com/read/29133150/structure-and-function-of-per-arnt-sim-domains-and-their-possible-role-in-the-life-cycle-biology-of-trypanosoma-cruzi
#1
REVIEW
Maura Rojas-Pirela, Daniel J Rigden, Paul A Michels, Ana J Cáceres, Juan Luis Concepción, Wilfredo Quiñones
Per-ARNT-Sim (PAS) domains of proteins play important roles as modules for signalling and cellular regulation processes in widely diverse organisms such as Archaea, Bacteria, protists, plants, yeasts, insects and vertebrates. These domains are present in many proteins where they are used as sensors of stimuli and modules for protein interactions. Characteristically, they can bind a broad spectrum of molecules. Such binding causes the domain to trigger a specific cellular response or to make the protein containing the domain susceptible to responding to additional physical or chemical signals...
November 10, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29119655/targeting-host-mitochondria-a-role-for-the-trypanosoma-cruzi-amastigote-flagellum
#2
Gaelle Lentini, Nicolas Dos Santos Pacheco, Barbara A Burleigh
Trypanosoma cruzi is the kinetoplastid protozoan parasite that causes human Chagas disease, a chronic disease with complex outcomes including severe cardiomyopathy and sudden death. In mammalian hosts, T. cruzi colonizes a wide range of tissues and cell types where it replicates within the host cell cytoplasm. Like all intracellular pathogens, T. cruzi amastigotes must interact with its immediate host cell environment in a manner that facilitates access to nutrients and promotes a suitable niche for replication and survival...
November 8, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29114029/rapid-selection-free-high-efficiency-genome-editing-in-protozoan-parasites-using-crispr-cas9-ribonucleoproteins
#3
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/29107954/distribution-and-identification-of-sand-flies-naturally-infected-with-leishmania-from-the-southeastern-peruvian-amazon
#4
Victor Zorrilla, Maxy B De Los Santos, Liz Espada, Rocío Del Pilar Santos, Roberto Fernandez, Albino Urquia, Craig A Stoops, Sarah-Blythe Ballard, Andres G Lescano, Gissella M Vásquez, Hugo O Valdivia
BACKGROUND: Cutaneous leishmaniasis (CL) is an important health problem in the New World affecting civilian and military populations that are frequently exposed in endemic settings. The Peruvian region of Madre de Dios located near the border with Brazil is one of the most endemic CL regions in South America with more than 4,451 reported cases between 2010 and 2015 according to the Peruvian epidemiology directorate. However, little is known regarding the diversity and distribution of sand fly vectors in this region...
November 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29107734/involvement-of-snare-protein-ykt6-in-glycosome-biogenesis-in-trypanosoma-brucei
#5
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
https://www.readbyqxmd.com/read/29107485/the-cryo-em-structure-of-a-novel-40s-kinetoplastid-specific-ribosomal-protein
#6
Jailson Brito Querido, Eder Mancera-Martínez, Quentin Vicens, Anthony Bochler, Johana Chicher, Angelita Simonetti, Yaser Hashem
Kinetoplastids are potentially lethal protozoan pathogens affecting more than 20 million people worldwide. There is a critical need for more specific targets for the development of safer anti-kinetoplastid therapeutic molecules that can replace the scarce and highly cytotoxic current drugs. The kinetoplastid ribosome represents a potential therapeutic target due to its relative structural divergence when compared with its human counterpart. However, several kinetoplastid-specific ribosomal features remain uncharacterized...
October 13, 2017: Structure
https://www.readbyqxmd.com/read/29105342/optimization-and-evaluation-of-antiparasitic-benzamidobenzoic-acids-as-inhibitors-of-kinetoplastid-hexokinase-1
#7
Daniel P Flaherty, Michael T Harris, Chad E Schroeder, Haaris Khan, Elizabeth Kahney, Amber Hackler, Stephen Patrick, Warren S Weiner, Jeffrey Aube, Elizabeth R Sharlow, James C Morris, Jennifer E Golden
Kinetoplastid-based infections are neglected diseases that represent a significant human health issue. Chemotherapeutic options are limited due to toxicity, parasite susceptibility, and poor patient compliance. In response, we studied a molecular target-directed approach involving intervention of hexokinase activity - a pivotal enzyme in parasite metabolism. A benzamidobenzoic acid hit with modest biochemical inhibition of Trypanosoma brucei hexokinase 1 (TbHK1, IC₅₀ = 9.1 μM), low mammalian cytotoxicity (IMR90, EC₅₀ > 25 μM), and no appreciable activity on whole BSF parasites was optimized to afford a probe with improved TbHK1 potency and, significantly, efficacy against whole BSF parasites (TbHK1, IC₅₀ = 0...
November 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29078369/extensive-flagellar-remodeling-during-the-complex-life-cycle-of-paratrypanosoma-an-early-branching-trypanosomatid
#8
Tomáš Skalický, Eva Dobáková, Richard J Wheeler, Martina Tesařová, Pavel Flegontov, Dagmar Jirsová, Jan Votýpka, Vyacheslav Yurchenko, Francisco J Ayala, Julius Lukeš
Paratrypanosoma confusum is a monoxenous kinetoplastid flagellate that constitutes the most basal branch of the highly diverse parasitic trypanosomatids, which include human pathogens Trypanosoma and Leishmania This makes Paratrypanosoma uniquely informative for the evolution of obligatory parasitism from free-living lifestyle and the evolution of human parasitism in some trypanosomatid lineages. It has typical promastigote morphology but also forms surface-attached haptomonads and amastigotes. Haptomonads form by attachment to a surface via a large bulge at the base of the flagellum, which is then remodeled into a thin attachment pad associated with flagellum shortening...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073503/euglenoid-pellicle-morphogenesis-and-evolution-in-light-of-comparative-ultrastructure-and-trypanosomatid-biology-semi-conservative-microtubule-strip-duplication-strip-shaping-and-transformation
#9
REVIEW
Thomas Cavalier-Smith
Uniquely in eukaryotes, euglenoid pellicles comprise longitudinal proteinaceous, epiplasmic strips underlain by microtubules. Contradictory interpretations of pellicle microtubule duplication and segregation assumed opposite microtubule polarity from kinetoplastid Euglenozoa and conservative microtubule segregation. Distigma shows new pellicle microtubules nucleating posteriorly as in trypanosomatids, unifying euglenoid and kinetoplastid pellicle morphogenesis, but strip-growth is unpolarised. Epiplasmic insertion and cutting make new strip junctions between alternating wide and narrow daughter strips that grow intussusceptively...
September 18, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/29050882/surface-glycans-a-therapeutic-opportunity-for-kinetoplastid-diseases-trends-in-parasitology-2017
#10
Víctor M Castillo-Acosta, Jan Balzarini, Dolores González-Pacanowska
No abstract text is available yet for this article.
October 16, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/29031216/description-of-neoparamoeba-longipodia-n-sp-and-a-new-strain-of-neoparamoeba-aestuarina-page-1970-amoebozoa-dactylopodida-from-deep-sea-habitats
#11
Ekaterina Volkova, Alexander Kudryavtsev
Two strains of lobose amoebae have been isolated from the deep-sea bottom sediments of the Sea of Japan (3.6km deep) and Western Atlantic Ocean (5.1km deep). Amoebae of both strains have a dactylopodial mophotype, intracellular kinetoplastid symbiont (Perkinsela-like organism) and have no microscales on the cell surface. The morphology and molecular data of the Sea of Japan strain allow us to unambiguously identify it as Neoparamoeba aestuarina (Page, 1970). At the same time, the Atlantic strain is described as a new species Neoparamoeba longipodia as it differs from other species of the genus Neoparamoeba in morphology and gene sequence data...
September 21, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/29023425/screening-a-natural-product-based-library-against-kinetoplastid-parasites
#12
Bilal Zulfiqar, Amy J Jones, Melissa L Sykes, Todd B Shelper, Rohan A Davis, Vicky M Avery
Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world's lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays...
October 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28967262/chemical-validation-of-methionyl-trna-synthetase-as-a-druggable-target-in-leishmania-donovani
#13
Leah S Torrie, Stephen Brand, David A Robinson, Eun Jung Ko, Laste Stojanovski, Frederick R C Simeons, Susan Wyllie, John Thomas, Lucy Ellis, Maria Osuna-Cabello, Ola Epemolu, Andrea Nühs, Jennifer Riley, Lorna MacLean, Sujatha Manthri, Kevin D Read, Ian H Gilbert, Alan H Fairlamb, Manu De Rycker
Methionyl-tRNA synthetase (MetRS) has been chemically validated as a drug target in the kinetoplastid parasite Trypanosoma brucei. In the present study, we investigate the validity of this target in the related trypanosomatid Leishmania donovani. Following development of a robust high-throughput compatible biochemical assay, a compound screen identified DDD806905 as a highly potent inhibitor of LdMetRS (Ki of 18 nM). Crystallography revealed this compound binds to the methionine pocket of MetRS with enzymatic studies confirming DDD806905 displays competitive inhibition with respect to methionine and mixed inhibition with respect to ATP binding...
October 13, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28935948/novel-scaffolds-for-inhibition-of-cruzipain-identified-from-high-throughput-screening-of-anti-kinetoplastid-chemical-boxes
#14
Emir Salas-Sarduy, Lionel Urán Landaburu, Joel X Karpiak, Kevin P Madauss, Juan José Cazzulo, Fernán Agüero, Vanina Eder Alvarez
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935112/a-pipeline-for-studying-and-engineering-single-subunit-oligosaccharyltransferases
#15
Thapakorn Jaroentomeechai, Xiaolu Zheng, Jasmine Hershewe, Jessica C Stark, Michael C Jewett, Matthew P DeLisa
Asparagine-linked (N-linked) protein glycosylation is one of the most abundant types of posttranslational modification, occurring in all domains of life. The central enzyme in N-linked glycosylation is the oligosaccharyltransferase (OST), which catalyzes the covalent attachment of preassembled glycans to specific asparagine residues in target proteins. Whereas in higher eukaryotes the OST is comprised of eight different membrane proteins, of which the catalytic subunit is STT3, in kinetoplastids and prokaryotes the OST is a monomeric enzyme bearing homology to STT3...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28916813/genome-sequencing-reveals-metabolic-and-cellular-interdependence-in-an-amoeba-kinetoplastid-symbiosis
#16
Goro Tanifuji, Ugo Cenci, Daniel Moog, Samuel Dean, Takuro Nakayama, Vojtěch David, Ivan Fiala, Bruce A Curtis, Shannon J Sibbald, Naoko T Onodera, Morgan Colp, Pavel Flegontov, Jessica Johnson-MacKinnon, Michael McPhee, Yuji Inagaki, Tetsuo Hashimoto, Steven Kelly, Keith Gull, Julius Lukeš, John M Archibald
Endosymbiotic relationships between eukaryotic and prokaryotic cells are common in nature. Endosymbioses between two eukaryotes are also known; cyanobacterium-derived plastids have spread horizontally when one eukaryote assimilated another. A unique instance of a non-photosynthetic, eukaryotic endosymbiont involves members of the genus Paramoeba, amoebozoans that infect marine animals such as farmed fish and sea urchins. Paramoeba species harbor endosymbionts belonging to the Kinetoplastea, a diverse group of flagellate protists including some that cause devastating diseases...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28913164/haemoprotozoa-making-biological-sense-of-molecular-phylogenies
#17
REVIEW
Peter O'Donoghue
A range of protistan parasites occur in the blood of vertebrates and are transmitted by haematophagous invertebrate vectors. Some 48 genera are recognized in bood primarily on the basis of parasite morphology and host specificity; including extracellular kinetoplastids (trypanosomatids) and intracellular apicomplexa (haemogregarines, haemococcidia, haemosporidia and piroplasms). Gene sequences are available for a growing number of species and molecular phylogenies often link parasite and host or vector evolution...
December 2017: International Journal for Parasitology. Parasites and Wildlife
https://www.readbyqxmd.com/read/28903536/an-alternative-strategy-for-trypanosome-survival-in-the-mammalian-bloodstream-revealed-through-genome-and-transcriptome-analysis-of-the-ubiquitous-bovine-parasite-trypanosoma-megatrypanum-theileri
#18
Steven Kelly, Alasdair Ivens, G Adam Mott, Ellis O'Neill, David Emms, Olivia Macleod, Paul Voorheis, Kevin Tyler, Matthew Clark, Jacqueline Matthews, Keith Matthews, Mark Carrington
There are hundreds of Trypanosoma species that live in the blood and tissue spaces of their vertebrate hosts. The vast majority of these do not have the ornate system of antigenic variation that has evolved in the small number of African trypanosome species, but can still maintain long-term infections in the face of the vertebrate adaptive immune system. Trypanosoma theileri is a typical example, has a restricted host range of cattle and other Bovinae, and is only occasionally reported to cause patent disease although no systematic survey of the effect of infection on agricultural productivity has been performed...
August 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28886510/polyamine-based-analogs-and-conjugates-as-antikinetoplastid-agents
#19
REVIEW
Elodie Jagu, Sébastien Pomel, Stéphanie Pethe, Philippe M Loiseau, Raphaël Labruère
Naturally occurring polyamines: putrescine, spermidine and spermine are crucial for Kinetoplastid growth and persistence. These aliphatic polycations are either biosynthesized or internalized into Kinetoplastid by active transport. Impairing the polyamine metabolism using polyamine derivatives is an interesting path in the search of new antikinetoplastid chemotherapy. In the past 30 years, research interest in this field has been constantly expanding and recent results demonstrated that the discovery of a polyamine-based antikinetoplastid drug is undoubtedly possible...
October 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28844893/tandem-affinity-purification-of-exosome-and-replication-factor-c-complexes-from-the-non-human-infectious-kinetoplastid-parasite-crithidia-fasciculata
#20
Wakisa Kipandula, Terry K Smith, Stuart A MacNeill
Kinetoplastid parasites are responsible for a range of diseases with significant global impact. Trypanosoma brucei and Trypanosoma cruzi cause human African trypanosomiasis and Chagas disease, respectively, while various Leishmania species are responsible for cutaneous, mucocutaneous and visceral leishmaniasis. Understanding the biology of these organisms is key for effective diagnosis, prophylaxis and treatment. The insect parasite Crithidia fasciculata offers a safe and low-cost alternative for studies of kinetoplastid biology...
October 2017: Molecular and Biochemical Parasitology
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