1,073 results match your criteria Kinetoplastid Biology and Disease [Journal]


The RRM of the kRNA-editing protein TbRGG2 uses multiple surfaces to bind and remodel RNA.

Nucleic Acids Res 2018 Dec 14. Epub 2018 Dec 14.

Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.

Kinetoplastid RNA (kRNA) editing takes place in the mitochondria of kinetoplastid protists and creates translatable mRNAs by uridine insertion/deletion. Extensively edited (pan-edited) transcripts contain quadruplex forming guanine stretches, which must be remodeled to promote uridine insertion/deletion. Here we show that the RRM domain of the essential kRNA-editing factor TbRGG2 binds poly(G) and poly(U) RNA and can unfold both. Read More

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December 2018

Drug Discovery for Kinetoplastid Diseases: Future Directions.

ACS Infect Dis 2018 Dec 13. Epub 2018 Dec 13.

Novartis Institute for Tropical Diseases (NITD) , 5300 Chiron Way , Emeryville , California 94608 , United States.

Kinetoplastid parasites have caused human disease for millennia. Significant achievements have been made toward developing new treatments for leishmaniasis (particularly on the Indian subcontinent) and for human African trypanosomiasis (HAT). Moreover, the sustained decrease in the incidence of HAT has made the prospect of elimination a tantalizing reality. Read More

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December 2018

The antibiotic resistance-free mammalian expression plasmid vector pPAL for development of third generation vaccines.

Plasmid 2018 Dec 6. Epub 2018 Dec 6.

Laboratory of Molecular Parasitology, Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (Consejo Superior de Investigaciones Científicas). Calle Ramiro de Maeztu, 9, 28040 Madrid, Spain. Electronic address:

DNA vaccines require a vector to replicate genes and express encoding antigens. Antibiotic resistance genes are often used as selection markers, which must not be released to the environment upon final product commercialization. For this reason, generation of antibiotic resistance-free vectors is imperative. Read More

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December 2018

Measurement of Tunic Hardness in an Edible Ascidian, Halocynthia roretzi, with Remarks on Soft Tunic Syndrome.

Zoolog Sci 2018 Dec;35(6):548-552

2 Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama, Ehime 790-8577, Japan.

The infection caused by a kinetoplastid flagellate, Azumiobodo hoyamushi, in an ascidian, Halocynthia roretzi, results in softening of the tunic, and finally death. This disease is usually recognized using palpation of the softening tunic, and A. hoyamushi infection is detectable using microscopy or PCR amplification of specific gene fragments. Read More

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December 2018
2 Reads

The Hsp70/J-protein machinery of the African trypanosome, Trypanosoma brucei.

Cell Stress Chaperones 2018 Dec 1. Epub 2018 Dec 1.

Biotechnology Innovation Centre, Rhodes University, Grahamstown, South Africa.

The etiological agent of the neglected tropical disease African trypanosomiasis, Trypanosoma brucei, possesses an expanded and diverse repertoire of heat shock proteins, which have been implicated in cytoprotection, differentiation, as well as progression and transmission of the disease. Hsp70 plays a crucial role in proteostasis, and inhibition of its interactions with co-chaperones is emerging as a potential therapeutic target for numerous diseases. In light of genome annotations and the release of the genome sequence of the human infective subspecies, an updated and current in silico overview of the Hsp70/J-protein machinery in both T. Read More

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December 2018
1 Read

Structural explanation for the tunable substrate specificity of an E. coli nucleoside hydrolase: insights from molecular dynamics simulations.

J Comput Aided Mol Des 2018 Dec 26;32(12):1375-1388. Epub 2018 Nov 26.

Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, AB, T1K 3M4, Canada.

Parasitic protozoa rely on nucleoside hydrolases that play key roles in the purine salvage pathway by catalyzing the hydrolytic cleavage of the N-glycosidic bond that connects nucleobases to ribose sugars. Cytidine-uridine nucleoside hydrolase (CU-NH) is generally specific toward pyrimidine nucleosides; however, previous work has shown that replacing two active site residues with Tyr, specifically the Thr223Tyr and Gln227Tyr mutations, allows CU-NH to process inosine. The current study uses molecular dynamics (MD) simulations to gain atomic-level insight into the activity of wild-type and mutant E. Read More

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December 2018

Allobodo chlorophagus n. gen. n. sp., a Kinetoplastid that Infiltrates and Feeds on the Invasive Alga Codium fragile.

Protist 2018 Dec 1;169(6):911-925. Epub 2018 Aug 1.

Department of Biology, and Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax B3H 4R2, Canada. Electronic address:

A novel biflagellate protist that consumed chloroplasts inside material of the invasive marine green alga Codium fragile was reported from the U.S. east coast in 2003. Read More

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December 2018
9 Reads

Unexpected Evolution of Lesion-Recognition Modules in Eukaryotic NER and Kinetoplast DNA Dynamics Proteins from Bacterial Mobile Elements.

iScience 2018 Nov 23;9:192-208. Epub 2018 Oct 23.

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. Electronic address:

The provenance of several components of major uniquely eukaryotic molecular machines are increasingly being traced back to prokaryotic biological conflict systems. Here, we demonstrate that the N-terminal single-stranded DNA-binding domain from the anti-restriction protein ArdC, deployed by bacterial mobile elements against their host, was independently acquired twice by eukaryotes, giving rise to the DNA-binding domains of XPC/Rad4 and the Tc-38-like proteins in the stem kinetoplastid. In both instances, the ArdC-N domain tandemly duplicated forming an extensive DNA-binding interface. Read More

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November 2018
3 Reads

Substrate specificity of the neutral sphingomyelinase from Trypanosoma brucei.

Parasitology 2018 Nov 5:1-13. Epub 2018 Nov 5.

Biomedical Sciences Research Complex,Schools of Biology and Chemistry,University of St Andrews,Fife, KY16 9ST,UK.

The kinetoplastid parasite Trypanosoma brucei causes African trypanosomiasis in both humans and animals. Infections place a significant health and economic burden on developing nations in sub-Saharan Africa, but few effective anti-parasitic treatments are currently available. Hence, there is an urgent need to identify new leads for drug development. Read More

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November 2018
4 Reads

Indirubin derivatives are potent and selective anti-Trypanosoma cruzi agents.

Virulence 2018 ;9(1):1658-1668

b Laboratory of Tissue Engineering and Immunopharmacology , Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ) , Salvador , BA , Brazil.

Current treatment for combatting Chagas disease, a life-threatening illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi is inadequate, and thus the discovery of new antiparasitic compounds is of prime importance. Previous studies identified the indirubins, a class of ATP kinase inhibitors, as potent growth inhibitors of the related kinetoplastid Leishmania. Herein, we evaluated the inhibitory activity of a series of 69 indirubin analogues screened against T. Read More

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January 2018
1 Read

Genomic comparison of Trypanosoma conorhini and Trypanosoma rangeli to Trypanosoma cruzi strains of high and low virulence.

BMC Genomics 2018 Oct 24;19(1):770. Epub 2018 Oct 24.

Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA, USA.

Background: Trypanosoma conorhini and Trypanosoma rangeli, like Trypanosoma cruzi, are kinetoplastid protist parasites of mammals displaying divergent hosts, geographic ranges and lifestyles. Largely nonpathogenic T. rangeli and T. Read More

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October 2018
6 Reads

Genome-wide identification of evolutionarily conserved Small Heat-Shock and eight other proteins bearing α-crystallin domain-like in kinetoplastid protists.

PLoS One 2018 22;13(10):e0206012. Epub 2018 Oct 22.

Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.

Small Heat-Shock Proteins (sHSPs) and other proteins bearing alpha-crystallin domains (ACD) participate in defense against heat and oxidative stress and play important roles in cell cycle, cytoskeleton dynamics, and immunological and pathological mechanisms in eukaryotes. However, little is known about these proteins in early-diverging lineages of protists such as the kinetoplastids. Here, ACD-like proteins (ACDp) were investigated in genomes of 61 species of 12 kinetoplastid genera, including Trypanosoma spp. Read More

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October 2018

Revisiting Trypanosome Mitochondrial Genome Mysteries: Broader and Deeper.

Authors:
Sara L Zimmer

Trends Parasitol 2018 Oct 9. Epub 2018 Oct 9.

University of Minnesota, Duluth, MN, USA. Electronic address:

What do the products of a genome do, and when and why are they needed? For the protein products of the trypanosomatid parasites' mitochondrial genomes, the total expressed protein repertoire and the identities of the more difficult-to-characterize products have been challenging to acquire. Comparative genomics and new technologies may resolve that. Read More

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October 2018

Crystal structure of an ENT domain from Trypanosoma brucei.

Biochem Biophys Res Commun 2018 Nov 4;505(3):755-760. Epub 2018 Oct 4.

Hefei National Laboratory for Physical Science at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, PR China. Electronic address:

Trypanosoma brucei (T. brucei) is a parasitic protozoan causing human sleeping sickness and related animal diseases. ENT (EMSY N-terminal) domain was first found in EMSY protein which has been proved to be involved in multiple biological processes such as DNA repair, tumorigenesis, and transcriptional regulation. Read More

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November 2018

Massive mitochondrial DNA content in diplonemid and kinetoplastid protists.

IUBMB Life 2018 Dec 6;70(12):1267-1274. Epub 2018 Oct 6.

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada.

The mitochondrial DNA of diplonemid and kinetoplastid protists is known for its suite of bizarre features, including the presence of concatenated circular molecules, extensive trans-splicing and various forms of RNA editing. Here we report on the existence of another remarkable characteristic: hyper-inflated DNA content. We estimated the total amount of mitochondrial DNA in four kinetoplastid species (Trypanosoma brucei, Trypanoplasma borreli, Cryptobia helicis, and Perkinsela sp. Read More

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December 2018

Gene Function Discovery for Kinetoplastid Pathogens.

Trends Parasitol 2018 Sep 28. Epub 2018 Sep 28.

Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.

We propose to integrate the existing and new experimental data with computational tools to model interaction networks for the most prominent kinetoplastid pathogens. These interaction networks will vastly expand the functional annotation of the kinetoplastid genomes, which in turn are critical for identifying new routes of disease intervention. Read More

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September 2018
4 Reads

Development of Chemical Proteomics for the Folateome and Analysis of the Kinetoplastid Folateome.

ACS Infect Dis 2018 Oct 28;4(10):1475-1486. Epub 2018 Sep 28.

Division of Biological Chemistry and Drug Discovery, College of Life Sciences , University of Dundee , Dundee , DD1 5EH , United Kingdom.

The folate pathway has been extensively studied in a number of organisms, with its essentiality exploited by a number of drugs. However, there has been little success in developing drugs that target folate metabolism in the kinetoplastids. Despite compounds being identified which show significant inhibition of the parasite enzymes, this activity does not translate well into cellular and animal models of disease. Read More

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October 2018

Targeting kinetoplastid and apicomplexan thymidylate biosynthesis as an antiprotozoal strategy.

Curr Med Chem 2018 Sep 26. Epub 2018 Sep 26.

Instituto de Parasitologia y Biomedicina "Lopez-Neyra", Consejo Superior de Investigaciones Cientificas, Granada. Spain.

Kinetoplastid and apicomplexan parasites comprise a group of protozoans responsible for human diseases, with a serious impact in human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms and nucleotide metabolism is considered a promising area for the provision of antimicrobial therapeutic targets. Impairment of thymidylate (dTMP) biosynthesis severely diminishes the viability of parasitic protozoa and the absence of enzymatic activities specifically involved in the formation of dTMP (e. Read More

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September 2018
7 Reads

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing.

PLoS Pathog 2018 Sep 25;14(9):e1007315. Epub 2018 Sep 25.

Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg, Germany.

Kinetoplastid parasites-trypanosomes and leishmanias-infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis. Read More

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September 2018

A systematic review of the Trypanosoma cruzi genetic heterogeneity, host immune response and genetic factors as plausible drivers of chronic chagasic cardiomyopathy.

Parasitology 2018 Sep 13:1-15. Epub 2018 Sep 13.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Programa de Biología,Facultad de Ciencias Naturales y Matemáticas,Universidad del Rosario,Bogotá,Colombia.

Chagas disease is a complex tropical pathology caused by the kinetoplastid Trypanosoma cruzi. This parasite displays massive genetic diversity and has been classified by international consensus in at least six Discrete Typing Units (DTUs) that are broadly distributed in the American continent. The main clinical manifestation of the disease is the chronic chagasic cardiomyopathy (CCC) that is lethal in the infected individuals. Read More

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September 2018
6 Reads

The kinetoplastid kinetochore protein KKT4 is an unconventional microtubule tip-coupling protein.

J Cell Biol 2018 Nov 12;217(11):3886-3900. Epub 2018 Sep 12.

Department of Biochemistry, University of Oxford, Oxford, UK

Kinetochores are multiprotein machines that drive chromosome segregation by maintaining persistent, load-bearing linkages between chromosomes and dynamic microtubule tips. Kinetochores in commonly studied eukaryotes bind microtubules through widely conserved components like the Ndc80 complex. However, in evolutionarily divergent kinetoplastid species such as , which causes sleeping sickness, the kinetochores assemble from a unique set of proteins lacking homology to any known microtubule-binding domains. Read More

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November 2018
16 Reads

Influence of 6-aminonicotinamide (6AN) on Leishmania promastigotes evaluated by metabolomics: Beyond the pentose phosphate pathway.

Chem Biol Interact 2018 Oct 29;294:167-177. Epub 2018 Aug 29.

Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialty Surgical Sciences, Via Borsari 46, University of Ferrara, 44121, Ferrara, Italy. Electronic address:

6-Aminonicotinamide (6AN) is an antimetabolite used to inhibit the NADPH-producing pentose phosphate pathway (PPP) in many cellular systems, making them more susceptible to oxidative stress. It is converted by a NAD(P) glycohydrolase to 6-aminoNAD and 6-aminoNADP, causing the accumulation of PPP intermediates, due to their inability to participate in redox reactions. Some parasites like Plasmodium falciparum and Coccidia are highly sensitive but not all cell types showed a strong responsiveness to 6AN, probably due to the different targeted pathway. Read More

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October 2018
1 Read

Tunic extract of the host ascidian attracts the causal agent of soft tunic syndrome, Azumiobodo hoyamushi (Kinetoplastea: Neobodonida).

Dis Aquat Organ 2018 08;129(3):207-214

Miyagi Prefecture Fisheries Technology Institute, Ishinomaki, Miyagi 986-2135, Japan.

Azumiobodo hoyamushi, a kinetoplastid flagellate, is the causative agent of soft tunic syndrome, an infectious disease of the edible ascidian Halocynthia roretzi. The flagellate is thought to invade the tunic matrix via a damaged area of the tunic on the siphon wall. We hypothesized that the flagellate locates the tunic entry site by a chemotactic response to soluble substances diffused from the host ascidians. Read More

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August 2018
6 Reads

The conserved hypothetical protein Tb427.10.13790 is required for cytokinesis in Trypanosoma brucei.

Acta Trop 2018 Dec 25;188:34-40. Epub 2018 Aug 25.

Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany; School of Medicine, Tongji University, Shanghai, China. Electronic address:

Trypanosoma brucei, a flagellated protozoan causing the deadly tropical disease Human African Trypanosomiasis (HAT), affects people in sub-Saharan Africa. HAT therapy relies upon drugs which use is limited by toxicity and rigorous treatment regimes, while development of vaccines remains elusive, due to the effectiveness of the parasite´s antigenic variation. Here, we evaluate a hypothetical protein Tb427. Read More

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December 2018
7 Reads

2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas' disease.

Bioorg Med Chem Lett 2018 Oct 3;28(18):3025-3030. Epub 2018 Aug 3.

Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom. Electronic address:

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8-10 million people across the Latin American population and is responsible for around 12,500 deaths per annum. The current frontline treatments, benznidazole and nifurtimox, are associated with side effects and lack efficacy in the chronic stage of the disease, leading to an urgent need for new treatments. A high throughput screening campaign against the physiologically relevant intracellular form of the parasite identified a series of 2,4-diamino-6-methylpyrimidines. Read More

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October 2018
3 Reads

Dynamic RNA holo-editosomes with subcomplex variants: Insights into the control of trypanosome editing.

Wiley Interdiscip Rev RNA 2018 11 12;9(6):e1502. Epub 2018 Aug 12.

Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

RNA editing causes massive remodeling of the mitochondrial mRNA transcriptome in trypanosomes and related kinetoplastid protozoa. This type of editing involves the specific insertion or deletion of uridylates (U) directed by small noncoding guide RNAs (gRNAs). Because U-insertion exceeds U-deletion by a factor of 10, editing increases the nascent mRNA size by up to 55%. Read More

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November 2018

Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents.

Bioorg Med Chem 2018 Aug 25;26(14):4065-4072. Epub 2018 Jun 25.

Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Avenida Colombo 5790, 87020-900 Maringá, PR, Brazil. Electronic address:

Continuous efforts have been made to discover new drugs for the treatment of Chagas' disease, human African trypanosomiasis, and leishmaniasis. We have previously reported the synthesis and antileishmanial and antitrypanosomal (Y strain) properties of 2,3-disubstituted quinoxalines. Considering their promising antiparasitic potential, the present study was conducted to expand our search and take advantage of high-throughput assays to investigate the effects of quinoxaline derivatives against Leishmania donovani, Trypanosoma brucei, and Trypanosoma cruzi (Tulahuen strain). Read More

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August 2018
1 Read

Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II, disrupts mitochondrial architecture in trypanosomatid parasites.

Sci Rep 2018 Aug 9;8(1):11940. Epub 2018 Aug 9.

Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, 700 032, India.

Kinetoplast DNA (kDNA) bearing unusual mitochondrion of trypanosomatid parasites offers a new paradigm in chemotherapy modality. Topoisomerase II of Leishmania donovani (LdTopII), a key enzyme associated with kDNA replication, is emerging as a potential drug target. However, mode of action of LdTopII targeted compounds in the parasites at sub-cellular level remains largely unknown. Read More

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Human Kinetoplastid Protozoan Infections: Where Are We Going Next?

Front Immunol 2018 25;9:1493. Epub 2018 Jul 25.

Immunoparasitology Laboratory, Oswaldo Cruz Foundation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.

Kinetoplastida trypanosomatidae microorganisms are protozoan parasites exhibiting a developmental stage in the gut of insect vectors and tissues of vertebrate hosts. During the vertebrate infective stages, these parasites alter the differential expression of virulence genes, modifying their biological and antigenic properties in order to subvert the host protective immune responses and establish a persistent infection. One of the hallmarks of kinetoplastid parasites is their evasion mechanisms from host immunity, leading to disease chronification. Read More

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July 2018
18 Reads

Guide RNA genes up-regulated in Leishmania infantum metacyclic promastigotes.

Acta Trop 2018 Nov 25;187:72-77. Epub 2018 Jul 25.

Departamento de Biología Celular y Molecular, Centro de Investigaciones Biológicas (CSIC), calle Ramiro de Maeztu 9, 28034 Madrid, Spain.

The kinetoplastid parasite Leishmania infantum is responsible for zoonotic visceral leishmaniasis in the mediterranean basin, where dogs are the reservoir. Differential gene expression analysis of metacyclic promastigotes in axenic culture by whole genome DNA microarray hybridization revealed up-regulation of two unidentified genes that are absent in the parasite's genome databases. Sequence analysis has revealed that these genes encode for guide RNAs (gRNAs), which are located in the kinetoplast and participate in the kinetoplastid-specific uridine insertion/deletion RNA editing process. Read More

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November 2018
5 Reads

First Nonphosphorylated Inhibitors of Phosphoglucose Isomerase Identified by Chemical Library Screening.

SLAS Discov 2018 Dec 11;23(10):1051-1059. Epub 2018 Jul 11.

1 Brazilian Bioscience National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, SP, Brazil.

Human African trypanosomiasis, Chagas disease, and leishmaniasis are human infections caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania. Besides their severity and global impact, treatments are still challenging. Currently available drugs have important limitations, highlighting the urgent need to develop new drugs. Read More

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December 2018
6 Reads

Population Structure of Causing Anthroponotic Cutaneous Leishmaniasis in Southern Iran by PCR-RFLP of Kinetoplastid DNA.

Biomed Res Int 2018 6;2018:6049198. Epub 2018 Jun 6.

Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Iran is one of the six countries with the most cutaneous leishmaniasis (CL) patients. Understanding better the genotypes of the parasite population in relation to geography and climate is critical to achieving better CL control. We aimed to characterise the population structure of , the cause of anthroponotic cutaneous leishmaniasis (ACL), from important foci in southeast (Bam and Kerman) and southwest (Shiraz) Iran. Read More

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June 2018
8 Reads

Evolution of protein trafficking in kinetoplastid parasites: Complexity and pathogenesis.

Traffic 2018 Nov 24;19(11):803-812. Epub 2018 Jul 24.

School of Life Sciences, University of Dundee, Dundee, UK.

The kinetoplastida and their close relatives are unicellular organisms prevalent within the biosphere and important for significant impacts on global health, economy and ecosystems. They are, under most models, an early branching lineage. Individual species adapted to highly diverse environments by adopting complex life styles; parasitic species can infect a wide range of eukaryotic hosts, while many relatives are free-living and some autotrophic from acquiring a plastid for photosynthesis. Read More

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November 2018
11 Reads

Faithful chromosome segregation in Trypanosoma brucei requires a cohort of divergent spindle-associated proteins with distinct functions.

Nucleic Acids Res 2018 Sep;46(16):8216-8231

Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, TX 77030, USA.

Faithful chromosome segregation depends on correct spindle microtubule-kinetochore attachment and requires certain spindle-associated proteins (SAPs) involved in regulating spindle dynamics and chromosome segregation. Little is known about the spindle-associated proteome in the early divergent Trypanosoma brucei and its roles in chromosome segregation. Here we report the identification of a cohort of divergent SAPs through localization-based screening and proximity-dependent biotin identification. Read More

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September 2018

Organometallic compounds in the discovery of new agents against kinetoplastid-caused diseases.

Eur J Med Chem 2018 Jul 1;155:459-482. Epub 2018 Jun 1.

Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale, Viale T. Michel 11, 15121, Alessandria, Italy. Electronic address:

The development of safe and affordable antiparasitic agents effective against neglected tropical diseases is a big challenge of the drug discovery. The drugs currently employed have limitations such as poor efficacy, drug resistance or side effects. Thus, the search for new promising drugs is more and more crucial. Read More

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July 2018
1 Read

Toward a Drug Against All Kinetoplastids: From LeishBox to Specific and Potent Trypanothione Reductase Inhibitors.

Mol Pharm 2018 Aug 27;15(8):3069-3078. Epub 2018 Jun 27.

Institute of Molecular Biology and Pathology, Italian National Research Council (IBPM CNR), Department of Biochemical Sciences , Sapienza University , P.le A. Moro 5 , 00185 Rome , Italy.

Leishmaniasis, Chagas disease, and sleeping sickness affect millions of people worldwide and lead to the death of about 50 000 humans per year. These diseases are caused by the kinetoplastids Leishmania, Trypanosoma cruzi, and Trypanosoma brucei, respectively. These parasites share many general features, including gene conservation, high amino acid identity among proteins, the presence of subcellular structures as glycosomes and the kinetoplastid, and genome architecture, that may make drug development family specific, rather than species-specific, i. Read More

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August 2018
6 Reads

Farming, slaving and enslavement: histories of endosymbioses during kinetoplastid evolution.

Parasitology 2018 Sep 13;145(10):1311-1323. Epub 2018 Jun 13.

Department of Biological Sciences,School of Applied Sciences, University of Huddersfield,Huddersfield, HD1 3DH,UK.

Parasitic trypanosomatids diverged from free-living kinetoplastid ancestors several hundred million years ago. These parasites are relatively well known, due in part to several unusual cell biological and molecular traits and in part to the significance of a few - pathogenic Leishmania and Trypanosoma species - as aetiological agents of serious neglected tropical diseases. However, the majority of trypanosomatid biodiversity is represented by osmotrophic monoxenous parasites of insects. Read More

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September 2018
2 Reads

Author Correction: Novel scaffolds for inhibition of Cruzipain identified from high-throughput screening of anti-kinetoplastid chemical boxes.

Sci Rep 2018 Jun 4;8(1):8743. Epub 2018 Jun 4.

Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico de Chascomús, Universidad Nacional de San Martín - CONICET, San Martin, B1650HMP, Buenos Aires, Argentina.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. Read More

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June 2018
1 Read

A FRET flow cytometry method for monitoring cytosolic and glycosomal glucose in living kinetoplastid parasites.

PLoS Negl Trop Dis 2018 05 31;12(5):e0006523. Epub 2018 May 31.

Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.

The bloodstream lifecycle stage of the kinetoplastid parasite Trypanosoma brucei relies solely on glucose metabolism for ATP production, which occurs in peroxisome-like organelles (glycosomes). Many studies have been conducted on glucose uptake and metabolism, but none thus far have been able to monitor changes in cellular and organellar glucose concentration in live parasites. We have developed a non-destructive technique for monitoring changes in cytosolic and glycosomal glucose levels in T. Read More

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A lentiviral vaccine expressing KMP11-HASPB fusion protein increases immune response to Leishmania major in BALB/C.

Parasitol Res 2018 Jul 29;117(7):2265-2273. Epub 2018 May 29.

Skin Diseases and Leishmaniasis Research Center, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania-specific protein that antibodies are produced against it in the sera of Leishmania-infected individuals. Kinetoplastid membrane protein 11 (KMP11) is another Leishmania antigen and considered as the suitable candidate for vaccine development Leishmaniasis. It is a highly conserved surface protein expressed in both promastigotes and amastigotes. Read More

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July 2018
3 Reads
2.330 Impact Factor

Screening of the MMV and GSK open access chemical boxes using a viability assay developed against the kinetoplastid Crithidia fasciculata.

Mol Biochem Parasitol 2018 06 18;222:61-69. Epub 2018 May 18.

Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. Electronic address:

Diseases caused by the pathogenic kinetoplastids continue to incapacitate and kill hundreds of thousands of people annually throughout the tropics and sub-tropics. Unfortunately, in the countries where these neglected diseases occur, financial obstacles to drug discovery and technical limitations associated with biochemical studies impede the development of new, safe, easy to administer and effective drugs. Here we report the development and optimisation of a Crithidia fasciculata resazurin viability assay, which is subsequently used for screening and identification of anti-crithidial compounds in the MMV and GSK open access chemical boxes. Read More

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Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

Mol Microbiol 2018 Aug 25;109(3):306-326. Epub 2018 Jul 25.

Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912, USA.

The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. Read More

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The trypanosome-specific protein CIF3 cooperates with the CIF1 protein to promote cytokinesis in .

J Biol Chem 2018 Jun 15;293(26):10275-10286. Epub 2018 May 15.

From the Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030

Cytokinesis, the terminal step in cell division, in the protist human pathogen occurs along the longitudinal axis from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior cell tip. This process is regulated by a signaling cascade composed of the Polo-like kinase homolog TbPLK, the Aurora B kinase homolog TbAUK1, and the trypanosome-specific CIF1-CIF2 protein complex. However, the regulatory mechanism and the signaling pathway for this unusual mode of cytokinesis remain poorly understood. Read More

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June 2018
8 Reads

The 14th International Workshops on Opportunistic Protists (IWOP 14).

J Eukaryot Microbiol 2018 Nov 25;65(6):934-939. Epub 2018 May 25.

Departments of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461.

The 14th International Workshops on Opportunistic Protists (IWOP-14) was held August 10-12, 2017 in Cincinnati, OH, USA. The IWOP meetings focus on opportunistic protists (OIs); for example, free-living amoebae, Pneumocystis spp., Cryptosporidium spp. Read More

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November 2018
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Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids.

Curr Top Med Chem 2018 ;18(5):321-368

Departamento de Quimica Organica, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires. CONICET, Buenos Aires, Argentina.

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. Read More

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July 2018
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REDIdb 3.0: A Comprehensive Collection of RNA Editing Events in Plant Organellar Genomes.

Front Plant Sci 2018 11;9:482. Epub 2018 Apr 11.

Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, Consiglio Nazionale delle Ricerche, Bari, Italy.

RNA editing is an important epigenetic mechanism by which genome-encoded transcripts are modified by substitutions, insertions and/or deletions. It was first discovered in kinetoplastid protozoa followed by its reporting in a wide range of organisms. In plants, RNA editing occurs mostly by cytidine (C) to uridine (U) conversion in translated regions of organelle mRNAs and tends to modify affected codons restoring evolutionary conserved aminoacid residues. Read More

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Flagellum inheritance in requires a kinetoplastid-specific protein phosphatase.

J Biol Chem 2018 Jun 17;293(22):8508-8520. Epub 2018 Apr 17.

From the Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030 and

causes sleeping sickness in humans and nagana in cattle in sub-Saharan Africa and alternates between its mammalian hosts and its insect vector, the tsetse fly. uses a flagellum for motility, cell division, and cell-cell communication. Proper positioning and attachment of the newly assembled flagellum rely on the faithful duplication and segregation of flagellum-associated cytoskeletal structures. Read More

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Catalytically important flavin linked through a phosphoester bond in a eukaryotic fumarate reductase.

Biochimie 2018 Jun 3;149:34-40. Epub 2018 Apr 3.

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia. Electronic address:

One of the three domains of kinetoplastid NADH:fumarate oxidoreductase (FRD) is homologous to bacterial flavin transferase that catalyzes transfer of FMN residue from FAD to threonine in flavoproteins. Leptomonas pyrrhocoris FRD produced in yeast cells, which lack flavin transferase gene in their proteome, reduces fumarate in the presence of NADH and contains an FMN residue covalently linked to a Ser9 residue. The conserved flavinylation motif of FRD, D(g/s)x(s/t)(s/g)AS, is similar to the Dxx(s/t)gAT motif recognized by flavin transferase in prokaryotic proteins. Read More

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June 2018
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Discovery of a quinoline-based phenyl sulfone derivative as an antitrypanosomal agent.

Bioorg Med Chem Lett 2018 05 24;28(9):1647-1651. Epub 2018 Mar 24.

Department of Chemistry, Jackson State University, Jackson, MS 39217, USA. Electronic address:

A series of natural products-based phenyl sulfone derivative and their property-based analogues were investigated as potential growth inhibitors of Trypanosoma brucei. Trypanosoma brucei is a kinetoplastid protozoan parasite that causes trypanosomiasis. In this work, we found that nopol- and quinoline-based phenyl sulfone derivative were the most active and selective for T. Read More

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May 2018
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The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most abundant giant viruses in the sea.

Elife 2018 Mar 27;7. Epub 2018 Mar 27.

Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.

Giant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant group of giant viruses in ocean metagenomes, and the first isolate of a klosneuvirus, a subgroup of the proposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastid . Read More

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March 2018
4 Citations
8.520 Impact Factor