keyword
https://read.qxmd.com/read/37950023/identification-of-a-unique-conserved-region-from-a-kinetoplastid-genome-of-leishmania-orientalis-formerly-named-leishmania-siamensis-strain-pcm2-in-thailand
#21
JOURNAL ARTICLE
Pornchai Anuntasomboon, Suradej Siripattanapipong, Sasimanas Unajak, Kiattawee Choowongkomon, Richard Burchmore, Saovanee Leelayoova, Mathirut Mungthin, Teerasak E-Kobon
Mitochondrial DNAs (mtDNAs) appear in almost all eukaryotic species and are useful molecular markers for phylogenetic studies and species identification. Kinetoplast DNAs (kDNAs) are structurally complex circular mtDNA networks in kinetoplastids, divided into maxicircles and minicircles. Despite several kDNAs of many Leishmania species being examined, the kDNAs of the new species, Leishmania orientalis (formerly named Leishmania siamensis) strain PCM2, have not been explored. This study aimed to investigate the maxicircle and minicircle DNAs of L...
November 10, 2023: Scientific Reports
https://read.qxmd.com/read/37940706/simultaneous-targeted-amplicon-deep-sequencing-and-library-preparation-for-a-time-and-cost-effective-universal-parasite-diagnostic-sequencing-approach
#22
JOURNAL ARTICLE
Mathilde Gondard, Meredith Lane, Joel Barratt, Eldin Talundzic, Yvonne Qvarnstrom
We recently described a targeted amplicon deep sequencing (TADS) strategy that utilizes a nested PCR targeting the 18S rDNA gene of blood-borne parasites. The assay facilitates selective digestion of host DNA by targeting enzyme restriction sites present in vertebrates but absent in parasites. This enriching of parasite-derived amplicon drastically reduces the proportion of host-derived reads during sequencing and results in the sensitive detection of several clinically important blood parasites including Plasmodium spp...
November 9, 2023: Parasitology Research
https://read.qxmd.com/read/37907177/inhibition-and-structural-insights-of-leishmanial-glutamyl-trna-synthetase-for-designing-potent-therapeutics
#23
JOURNAL ARTICLE
Bandigi Narsimulu, Pranay Jakkula, Rahila Qureshi, Fouzia Nasim, Insaf Ahmed Qureshi
Aminoacyl-tRNA synthetases (aaRSs), essential components of the protein synthesizing machinery, have been often chosen for devising therapeutics against parasitic diseases. Due to their relevance in drug development, the current study was designed to explore functional and structural aspects of Leishmania donovani glutamyl-tRNA synthetase (LdGluRS). Hence, LdGluRS was cloned into an expression vector and purified to homogeneity using chromatography techniques. Purified protein showed maximum enzymatic activity at physiological pH, with more binding capacity towards its cofactor (Adenosine triphosphate, 0...
October 29, 2023: International Journal of Biological Macromolecules
https://read.qxmd.com/read/37906637/bromodomain-factor-5-as-a-target-for-antileishmanial-drug-discovery
#24
JOURNAL ARTICLE
Catherine N Russell, Jennifer L Carter, Juliet M Borgia, Jacob Bush, Félix Calderón, Raquel Gabarró, Stuart J Conway, Jeremy C Mottram, Anthony J Wilkinson, Nathaniel G Jones
Leishmaniases are a collection of neglected tropical diseases caused by kinetoplastid parasites in the genus Leishmania . Current chemotherapies are severely limited, and the need for new antileishmanials is of pressing international importance. Bromodomains are epigenetic reader domains that have shown promising therapeutic potential for cancer therapy and may also present an attractive target to treat parasitic diseases. Here, we investigate Leishmania donovani bromodomain factor 5 ( Ld BDF5) as a target for antileishmanial drug discovery...
October 31, 2023: ACS Infectious Diseases
https://read.qxmd.com/read/37760758/antimicrobial-peptides-amp-in-the-cell-free-culture-media-of-xenorhabdus-budapestensis-and-x-szentirmaii-exert-anti-protist-activity-against-eukaryotic-vertebrate-pathogens-including-histomonas-meleagridis-and-leishmania-donovani-species
#25
JOURNAL ARTICLE
András Fodor, Claudia Hess, Petra Ganas, Zsófia Boros, János Kiss, László Makrai, Károly Dublecz, László Pál, László Fodor, Anna Sebestyén, Michael G Klein, Eustachio Tarasco, Manjusha M Kulkarni, Bradford S McGwire, Tibor Vellai, Michael Hess
Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic-nematode species, release a series of non-ribosomal templated anti-microbial peptides. Some may be potential drug candidates. The ability of an entomopathogenic-nematode/entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product...
September 19, 2023: Antibiotics
https://read.qxmd.com/read/37730435/translational-control-by-trypanosoma-brucei-drbd18-contributes-to-the-maintenance-of-the-procyclic-state
#26
JOURNAL ARTICLE
Martin Ciganda, Jose Sotelo-Silveira, Ashutosh P Dubey, Parul Pandey, Joseph T Smith, Shichen Shen, Jun Qu, Pablo Smircich, Laurie K Read
Trypanosoma brucei occupies distinct niches throughout its life cycle, within both the mammalian and tsetse fly hosts. The immunological and biochemical complexity and variability of each of these environments require a reshaping of the protein landscape of the parasite both to evade surveillance and face changing metabolic demands. In kinetoplastid protozoa, including T. brucei, post-transcriptional control mechanisms are the primary means of gene regulation, and these are often mediated by RNA-binding proteins...
September 20, 2023: RNA
https://read.qxmd.com/read/37729272/disruption-of-the-inositol-phosphorylceramide-synthase-gene-affects-trypanosoma-cruzi-differentiation-and-infection-capacity
#27
JOURNAL ARTICLE
Nailma S Aprigio-Santos, Carlos F Estevez-Castro, Juan P Macedo, Daniela F Chame, Thiago Castro-Gomes, Mariana Santos-Cardoso, Gabriela A Burle-Caldas, Courtney N Covington, Patrick G Steel, Terry K Smith, Paul W Denny, Santuza M R Teixeira
Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T...
September 20, 2023: PLoS Neglected Tropical Diseases
https://read.qxmd.com/read/37729094/synthesis-and-biophysical-and-biological-studies-of-n-phenylbenzamide-derivatives-targeting-kinetoplastid-parasites
#28
JOURNAL ARTICLE
J Jonathan Nué-Martinez, David Cisneros, María Del Valle Moreno-Blázquez, Cristina Fonseca-Berzal, José Ignacio Manzano, Damien Kraeutler, Marzuq A Ungogo, Maha A Aloraini, Hamza A A Elati, Alexandra Ibáñez-Escribano, Laura Lagartera, Tomás Herraiz, Francisco Gamarro, Harry P de Koning, Alicia Gómez-Barrio, Christophe Dardonville
The AT-rich mitochondrial DNA (kDNA) of trypanosomatid parasites is a target of DNA minor groove binders. We report the synthesis, antiprotozoal screening, and SAR studies of three series of analogues of the known antiprotozoal kDNA binder 2-((4-(4-((4,5-dihydro-1 H -imidazol-3-ium-2-yl)amino)benzamido)phenyl)amino)-4,5-dihydro-1 H -imidazol-3-ium ( 1a ). Bis(2-aminoimidazolines) (1) and bis(2-aminobenzimidazoles) (2) showed micromolar range activity against Trypanosoma brucei, whereas bisarylimidamides (3) were submicromolar inhibitors of T...
September 20, 2023: Journal of Medicinal Chemistry
https://read.qxmd.com/read/37713416/strasseriolides-display-in-vitro-and-in-vivo-activity-against-trypanosomal-parasites-and-cause-morphological-and-size-defects-in-trypanosoma-cruzi
#29
JOURNAL ARTICLE
Cristina Bosch-Navarrete, Guiomar Pérez-Moreno, Frederick Annang, Rosario Diaz-Gonzalez, Raquel García-Hernández, Hedy Rocha, Francisco Gamarro, Carlos Cordón-Obras, Miguel Navarro, Ana Rodriguez, Olga Genilloud, Fernando Reyes, Francisca Vicente, Luis M Ruiz-Pérez, Dolores González-Pacanowska
Neglected diseases caused by kinetoplastid parasites are a health burden in tropical and subtropical countries. The need to create safe and effective medicines to improve treatment remains a priority. Microbial natural products are a source of chemical diversity that provides a valuable approach for identifying new drug candidates. We recently reported the discovery and bioassay-guided isolation of a novel family of macrolides with antiplasmodial activity. The novel family of four potent antimalarial macrolides, strasseriolides A-D, was isolated from cultures of Strasseria geniculata CF-247251, a fungal strain obtained from plant tissues...
September 15, 2023: PLoS Neglected Tropical Diseases
https://read.qxmd.com/read/37697722/computational-evaluation-of-phytochemicals-targeting-dna-topoisomerase-i-in-leishmania-donovani-molecular-docking-and-molecular-dynamics-simulation-studies
#30
JOURNAL ARTICLE
Praffulla Kumar Arya, Pranabesh Mandal, Krishnendu Barik, Durg Vijay Singh, Anil Kumar
DNA topoisomerase I (Topo I) is a ubiquitous enzyme that plays a crucial role in resolving the topological constraints of supercoiled DNA during various cellular activities, including repair, replication, recombination, transcription, and chromatin remodeling. Multiple studies have confirmed the essential role of Topo I in nucleic acid metabolism of Leishmania donovani , the kinetoplastid parasite responsible for visceral leishmaniasis or kala-azar. Inhibition of this enzyme has shown promise as a strategy for therapy against visceral leishmaniasis...
September 11, 2023: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/37682970/use-of-sera-cell-free-dna-cfdna-and-exovesicle-dna-for-the-molecular-diagnosis-of-chronic-chagas-disease
#31
JOURNAL ARTICLE
Noelia Lozano, Mercedes Gomez Samblas, Eva Calabuig, María José Giménez Martí, Maria Dolores Gómez Ruiz, José Miguel Sahuquillo Arce, Sergio Sequera-Arquelladas, José Miguel Molina Moreno, M Trelis, Antonio Osuna
Chagas disease, a neglected tropical disease, is now considered a worldwide health concern as a result of migratory movements from Central and South America to other regions that were considered free of the disease, and where the epidemiological risk is limited to transplacental transmission or blood or organ donations from infected persons. Parasite detection in chronically ill patients is restricted to serological tests that only determine infection by previous infection and not the presence of the parasite, especially in patients undergoing treatment evaluation or in newborns...
2023: PloS One
https://read.qxmd.com/read/37674581/a-nuclear-orthologue-of-the-dntp-triphosphohydrolase-samhd1-controls-dntp-homeostasis-and-genomic-stability-in-trypanosoma-brucei
#32
JOURNAL ARTICLE
Pablo Antequera-Parrilla, Víctor M Castillo-Acosta, Cristina Bosch-Navarrete, Luis Miguel Ruiz-Pérez, Dolores González-Pacanowska
Maintenance of dNTPs pools in Trypanosoma brucei is dependent on both biosynthetic and degradation pathways that together ensure correct cellular homeostasis throughout the cell cycle which is essential for the preservation of genomic stability. Both the salvage and de novo pathways participate in the provision of pyrimidine dNTPs while purine dNTPs are made available solely through salvage. In order to identify enzymes involved in degradation here we have characterized the role of a trypanosomal SAMHD1 orthologue denominated TbHD82...
2023: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/37600222/the-critical-role-of-mode-of-action-studies-in-kinetoplastid-drug-discovery
#33
JOURNAL ARTICLE
Alan H Fairlamb, Susan Wyllie
Understanding the target and mode of action of compounds identified by phenotypic screening can greatly facilitate the process of drug discovery and development. Here, we outline the tools currently available for target identification against the neglected tropical diseases, human African trypanosomiasis, visceral leishmaniasis and Chagas' disease. We provide examples how these tools can be used to identify and triage undesirable mechanisms, to identify potential toxic liabilities in patients and to manage a balanced portfolio of target-based campaigns...
May 10, 2023: Front Drug Discov (Lausanne)
https://read.qxmd.com/read/37548427/aak1-like-a-putative-pseudokinase-with-potential-roles-in-cargo-uptake-in-bloodstream-form-trypanosoma-brucei-parasites
#34
JOURNAL ARTICLE
Jennifer A Black, Christen M Klinger, Leandro Lemgruber, Joel B Dacks, Jeremy C Mottram, Richard McCulloch
Selection and internalization of cargo via clathrin-mediated endocytosis requires adaptor protein complexes. One complex, AP-2, acts during cargo selection at the plasma membrane. African trypanosomes lack all components of the AP-2 complex, except for a recently identified orthologue of the AP-2-associated protein kinase 1, AAK1. In characterized eukaryotes, AAK1 phosphorylates the μ2 subunit of the AP-2 complex to enhance cargo recognition and uptake into clathrin-coated vesicles. Here, we show that kinetoplastids encode not one, but two AAK1 orthologues: one (AAK1L2) is absent from salivarian trypanosomes, while the other (AAK1L1) lacks important kinase-specific residues in a range of trypanosomes...
August 7, 2023: Journal of Eukaryotic Microbiology
https://read.qxmd.com/read/37487087/unnexin-is-a-protein-subunit-of-a-large-pore-channel-expressed-by-unicellular-organisms
#35
JOURNAL ARTICLE
Juan Güiza, Francisco Solís, Bernardita Valenzuela, Duxan Arancibia, Pedro Zamorano, Jorge González, Jonathan Saavedra, Alan Neely, Magdiel Salgado, Agustín D Martínez, Juan C Sáez, José L Vega
Cells of vertebrate and invertebrate organisms express proteins specialized in membrane channel-based cell-cell communication that are absent in unicellular organisms. We recently described the prediction of some members of the large-pore channel family in kinetoplastids, consisting of proteins called unnexins, which share several structural features with innexin and pannexin proteins. Here, we demonstrated that the unnexin1 protein (Unx1) is delivered to the cell membrane, displaying a topology consisting of four transmembrane domains with C and N termini on the cytoplasmic side and form large-pore channels that are permeable to small molecules...
August 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/37479612/development-of-chimeric-protein-as-a-multivalent-vaccine-for-human-kinetoplastid-infections-chagas-disease-and-leishmaniasis
#36
JOURNAL ARTICLE
Marianna de Carvalho Clímaco, Luiza Almeida de Figueiredo, Rayane Cristina Lucas, Guilherme Rafael Gomide Pinheiro, Luísa Mourão Dias Magalhães, Ana Laura Grossi de Oliveira, Raquel Martins Almeida, Fernando Sérgio Barbosa, Daniella Castanheira Bartholomeu, Lilian Lacerda Bueno, Tiago Antonio Mendes, Bin Zhan, Kathryn Marie Jones, Peter Hotez, Maria Elena Bottazzi, Fabrício Marcus Silva Oliveira, Ricardo Toshio Fujiwara
Leishmania spp. and Trypanosoma cruzi are parasitic kinetoplastids of great medical and epidemiological importance since they are responsible for thousands of deaths and disability-adjusted life-years annually, especially in low- and middle-income countries. Despite efforts to minimize their impact, current prevention measures have failed to fully control their spread. There are still no vaccines available. Taking into account the genetic similarity within the Class Kinetoplastida, we selected CD8+ T cell epitopes preserved among Leishmania spp...
July 19, 2023: Vaccine
https://read.qxmd.com/read/37475965/novel-kinetoplastid-specific-camp-binding-proteins-identified-by-rnai-screening-for-camp-resistance-in-trypanosoma-brucei
#37
JOURNAL ARTICLE
Sabine Bachmaier, Matthew K Gould, Eleni Polatoglou, Radoslaw Omelianczyk, Ana E Brennand, Maha A Aloraini, Jane C Munday, David Horn, Michael Boshart, Harry P de Koning
Cyclic AMP signalling in trypanosomes differs from most eukaryotes due to absence of known cAMP effectors and cAMP independence of PKA. We have previously identified four genes from a genome-wide RNAi screen for resistance to the cAMP phosphodiesterase (PDE) inhibitor NPD-001. The genes were named cAMP Response Protein (CARP) 1 through 4. Here, we report an additional six CARP candidate genes from the original sample, after deep sequencing of the RNA interference target pool retrieved after NPD-001 selection (RIT-seq)...
2023: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/37427792/histone-divergence-in-trypanosomes-results-in-unique-alterations-to-nucleosome-structure
#38
JOURNAL ARTICLE
Gauri Deák, Hannah Wapenaar, Gorka Sandoval, Ruofan Chen, Mark R D Taylor, Hayden Burdett, James A Watson, Maarten W Tuijtel, Shaun Webb, Marcus D Wilson
Eukaryotes have a multitude of diverse mechanisms for organising and using their genomes, but the histones that make up chromatin are highly conserved. Unusually, histones from kinetoplastids are highly divergent. The structural and functional consequences of this variation are unknown. Here, we have biochemically and structurally characterised nucleosome core particles (NCPs) from the kinetoplastid parasite Trypanosoma brucei. A structure of the T. brucei NCP reveals that global histone architecture is conserved, but specific sequence alterations lead to distinct DNA and protein interaction interfaces...
July 10, 2023: Nucleic Acids Research
https://read.qxmd.com/read/37367658/laurequinone-a-lead-compound-against-leishmania
#39
JOURNAL ARTICLE
Sara García-Davis, Atteneri López-Arencibia, Carlos J Bethencourt-Estrella, Desirée San Nicolás-Hernández, Ezequiel Viveros-Valdez, Ana R Díaz-Marrero, José J Fernández, Jacob Lorenzo-Morales, José E Piñero
Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii have been studied for this purpose...
May 30, 2023: Marine Drugs
https://read.qxmd.com/read/37353138/a-trypanosoma-cruzi-phosphoglycerate-kinase-isoform-with-a-per-arnt-sim-domain-acts-as-a-possible-sensor-for-intracellular-conditions
#40
JOURNAL ARTICLE
Maura Rojas-Pirela, Andrea Delgado, Yossmayer D C Rondón-Guerrero, Ana J Cáceres, Paul A M Michels, Juan Luis Concepción, Wilfredo Quiñones
Per-ARNT-Sim (PAS) domains constitute a family of domains present in a wide variety of prokaryotic and eukaryotic organisms. They form part of the structure of various proteins involved in diverse cellular processes. Regulation of enzymatic activity and adaptation to environmental conditions, by binding small ligands, are the main functions attributed to PAS-containing proteins. Recently, genes for a diverse set of proteins with a PAS domain were identified in the genomes of several protists belonging to the group of kinetoplastids, however, until now few of these proteins have been characterized...
June 21, 2023: Experimental Parasitology
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