Article
Microbiology
Anuj Tripathi, Ujjal K. Singha, Ayorinde Cooley, Taneisha Gillyard, Evan Krystofiak, Siddharth Pratap, Jamaine Davis, Minu Chaudhuri
Summary: TbTim50 is essential for mitochondrial function, regulation of kDNA replication, and the cell cycle in the bloodstream form of T. brucei. Depletion of TbTim50 results in inhibited cell growth, changes in morphology, increased AMPK phosphorylation, and upregulation of stumpy marker genes. TbTim50 is a crucial therapeutic target for African trypanosomiasis.
Article
Microbiology
Marina Schock, Steffen Schmidt, Klaus Ersfeld
Summary: Trypanosome brucei, the causative agent of African sleeping sickness, has a highly ordered subpellicular microtubule cytoskeleton associated with various proteins regulating morphology, motility, and virulence. Identified protein CAP50 colocalises with microtubules but not with the flagellum, playing a crucial role in maintaining cellular integrity. Depletion of CAP50, along with CAP52 and CAP42, results in defects in cytokinesis, morphology, and microtubule organization.
Article
Multidisciplinary Sciences
Suad Gazi Jaafer Husaine Al Kufi, Josiah Emmerson, Heidi Rosenqvist, Catarina Mateus Moreira Garcia, Diana Onodelia Rios-Szwed, Martin Wiese
Summary: Kinesins, including LmxKIN29, play important roles in cell division, intracellular organization, and flagellum formation and maintenance. The study suggests that LmxKIN29 is a potential drug target for leishmaniasis based on its crucial role in the disease and its divergence from mammalian kinesins.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Marisa Actis, Naoaki Fujii, Zachary B. Mackey
Summary: PCNA is a protein complex that regulates DNA metabolic processes and cell functions through interactions with other proteins. Overproduction of PCNA in Trypanosoma brucei inhibits cell proliferation. This study aims to restore cell proliferation in the pathogen by disrupting interactions in the SLiM-binding pocket. Two bioactive compounds were discovered in the assay.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Biochemistry & Molecular Biology
Masayuki Nakanishi, Mami Hino, Hiroshi Nomoto
Summary: In this study, a null mutant of the SAH hydrolase gene was created in Trypanosoma brucei and surprisingly, despite the observed SAH accumulation, the mutant exhibited normal cell proliferation. This suggests that inhibiting SAH hydrolase may not be an effective approach to suppressing T. brucei proliferation, making the enzyme a less promising target for antitrypanosome drug development.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Xiaoxu Li, Juntao Lu, Lei Liu, Fei Li, Tongxin Xu, Liying Chen, Zhaoyang Yan, Yan Li, Wei Guo
Summary: Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with poor prognosis. Forkhead box K1 (FOXK1), a transcription factor, has been found to play a significant role in ESCC progression. Elevated FOXK1 expression levels were correlated with advanced disease stage and enhanced aggressive behavior of ESCC cells. Silencing FOXK1 resulted in improved radiosensitivity by impairing DNA damage repair and inducing cell cycle arrest and apoptosis. FOXK1 directly activated the transcription of CDC25A and CDK4, and knockdown of these genes reversed the biological effects mediated by FOXK1 overexpression.
SCIENTIFIC REPORTS
(2023)
Review
Immunology
Maria Gabriela Libisch, Natalia Rego, Carlos Robello
Summary: Chagas Disease is caused by the complex taxon T. cruzi, affecting nearly eight million people worldwide. T. cruzi has the ability to infect and interact with almost any nucleated cell, triggering molecular signaling cascades that depend on cell type, strain, and experimental variables. Host cell responses to infection, particularly in the respiratory chain and oxidative phosphorylation, vary depending on the T. cruzi strain and experimental model, while some responses remain consistent across strains, cell types, and conditions.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Caroline E. Dewar, Aitor Casas-Sanchez, Constentin Dieme, Aline Crouzols, Lee R. Haines, Alvaro Acosta-Serrano, Brice Rotureau, Achim Schnaufer
Summary: This study demonstrates that efficient energy production through mitochondria is critical for the trypanosome's swimming ability and migration within the tsetse fly. Surprisingly, trypanosomes with impaired mitochondrial energy production are only mildly compromised in their ability to colonize the tsetse fly midgut. This study provides new insights into the complex mechanisms of trypanosome infection in tsetse flies.
Article
Cell Biology
Hee-Sook Kim
Summary: In Trypanosoma brucei, genes are arranged in polycistronic transcription units, with transcription termination sites being crucial for controlling mRNA production. Three chromatin factors, H3v, H4v, and base J, contribute to the regulation of transcription termination sites in a coordinated manner, with H4v playing a major role in this process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Marlies Vanden Bempt, Koen Debackere, Sofie Demeyer, Quentin Van Thillo, Nienke Meeuws, Cristina Prieto, Sarah Provost, Nicole Mentens, Kris Jacobs, Olga Gielen, David Nittner, Seishi Ogawa, Keisuke Kataoka, Carlos Graux, Thomas Tousseyn, Jan Cools, Daan Dierickx
Summary: Peripheral T-cell lymphoma (PTCL) is a group of hematological cancers originating from the malignant transformation of mature T cells. A study has found that MYCN overexpression is a common characteristic of PTCL cases, and EZH2 is identified as a key downstream target of MYCN. Mouse models have demonstrated that MYCN-driven T-cell lymphoma is sensitive to EZH2 degradation or CDK1 inhibition, and shows synergy with histone deacetylase (HDAC) inhibitors.
Article
Multidisciplinary Sciences
Emma M. Briggs, Federico Rojas, Richard McCulloch, Keith R. Matthews, Thomas D. Otto
Summary: This study models the developmental steps of Trypanosoma brucei using oligopeptide-induced differentiation in vitro, capturing the transcriptomes of parasites through single cell transcriptomics. It details the relative order of biological events during asynchronous development, profiles dynamic gene expression patterns, identifies putative regulators, and provides a paradigm for dissecting differentiation events in parasites.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Caroline E. Dewar, Aitor Casas-Sanchez, Constentin Dieme, Aline Crouzols, Lee R. Haines, Alvaro Acosta-Serrano, Brice Rotureau, Achim Schnaufer
Summary: The single-celled parasite Trypanosoma brucei is transmitted by tsetse flies and its development in the fly's gut depends on efficient energy production by mitochondria.
Article
Infectious Diseases
Nofar Baron, Nitin Tupperwar, Irit Dahan, Uzi Hadad, Geula Davidov, Raz Zarivach, Michal Shapira
Summary: Leishmania parasites cycle between sand-fly vectors and mammalian hosts, adapting to changing environments through stage-specific gene expression regulation. Translation initiation is controlled post-transcriptionally in Leishmania, with LeishIF4E2 showing unique characteristics and functions that differ from other translation factors. Deletion of one LeishIF4E2 gene copy led to altered morphology, changes in proteome profiles, and impaired infectivity in macrophages, suggesting specific functions for individual LeishIF4Es.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Multidisciplinary Sciences
Alyssa M. Klein, Lynn Biderman, David Tong, Bita Alaghebandan, Sakina A. Plumber, Helen S. Mueller, Anne van Vlimmeren, Chen Katz, Carol Prives
Summary: This study suggests that MDM2 and MDMX may play a p53-independent role in maintaining cell-cycle progression by affecting the activity of E2F family members and p73, making them a potential target of interest in cancers lacking wild-type p53.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Larissa Melo do Nascimento, Franziska Egler, Katharina Arnold, Nina Papavasiliou, Christine Clayton, Esteban Erben
Summary: The study identified CFB2 as a crucial protein for stabilizing VSG mRNA, described cis acting elements within the VSG 3'-untranslated region that regulate the interaction, identified trans-acting factors present in the VSG messenger ribonucleoprotein particle, and mechanistically explained how CFB2 stabilizes the mRNA of this key pathogenicity factor. The approach used in this study has the potential to provide detailed biological insight into the metabolism of relatively abundant mRNAs in any eukaryote.
Article
Biochemical Research Methods
Cher P. Ooi, Corinna Benz, Michael D. Urbaniak
JOURNAL OF PROTEOMICS
(2020)
Review
Biochemistry & Molecular Biology
Freya Ferguson, Alexander G. McLennan, Michael D. Urbaniak, Nigel J. Jones, Nikki A. Copeland
FRONTIERS IN MOLECULAR BIOSCIENCES
(2020)
Article
Multidisciplinary Sciences
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Narissara Jariyapan, Godwin Kwakye-Nuako, Vanete Thomaz Soccol, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: The study provides raw and processed data from genome sequencing of isolates from six species of parasites. The data has been deposited in various databases and repositories, serving as a resource for comparative genomics and applications in parasitology.
Article
Microbiology
Santiago Chavez, Michael D. Urbaniak, Corinna Benz, Pablo Smircich, Beatriz Garat, Jose R. Sotelo-Silveira, Maria Ana Duhagon
Summary: Through ribosome profiling and proteomics, we investigated the posttranscriptional regulatory events at the replicative entrance of T. cruzi, revealing translational regulation and proteome changes. This study provides the first simultaneous assessment of the transcriptome, translatome, and proteome of trypanosomatids, highlighting the importance of translational and proteomic changes in the gene expression chronology during the cell cycle.
Article
Microbiology
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Narissara Jariyapan, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: Leishmania (Mundinia) orientalis is a kinetoplastid parasite first isolated in Thailand in 2014. The complete genome sequence of L (M.) orientalis, sequenced using combined short-read and long-read technologies, will facilitate greater understanding of this novel pathogen and its relationship to other members of the subgenus Mundinia.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)
Article
Microbiology
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Narissara Jariyapan, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: The study reports the first complete genome of Leishmania martiniquensis from Asia, providing insights into the evolution of the subgenus Mundinia.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)
Article
Microbiology
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Narissara Jariyapan, Godwin Kwakye-Nuako, Vanete Thomaz-Soccol, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: The LGAAP computational pipeline was able to assemble six genomes of the parasite subfamily Leishmaniinae to chromosome-scale completeness, using a combination of long- and short-read sequencing data. LGAAP is open source and can be easily adapted for assembly of genomes of similar size (around 35 Mb).
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)
Article
Microbiology
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Vanete Thomaz-Soccol, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: Leishmania (Mundinia) enriettii, a parasitic kinetoplastid first isolated in 1946, has had its complete genome sequenced to enhance understanding of genome diversity within the species.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)
Article
Microbiology
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Godwin Kwakye-Nuako, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: Leishmania (Mundinia) sp. Ghana is a kinetoplastid parasite discovered in Ghana in 2015. The complete genome sequence of L. (M.) sp. Ghana was reported using a combination of short-read and long-read technologies, which will aid in understanding this novel pathogen and its relationships within the subgenus Mundinia.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)
Article
Microbiology
Hatim Almutairi, Michael D. Urbaniak, Michelle D. Bates, Waleed S. Al-Salem, Rod J. Dillon, Paul A. Bates, Derek Gatherer
Summary: Porcisia hertigi, a parasitic kinetoplastid first isolated from porcupines in central Panama in 1965, has had its complete genome sequence presented for isolate C119, strain LV43, using both short- and long-read technologies. This genome sequence will enhance our understanding of the parasitic genus Porcisia.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)
Article
Biochemistry & Molecular Biology
Corinna Benz, Nora Muller, Sabine Kaltenbrunner, Hana Vachova, Marie Vancova, Julius Lukes, Vladimir Varga, Hassan Hashimi
Summary: In this study, a characterization of an orphaned X2 kinesin in Trypanosoma brucei was conducted. It was found that this kinesin interacts tightly with a likely inactive motor-like protein, TbPH1, and localizes to a poorly understood cytoskeletal structure called the microtubule quartet (MtQ). Another X2 kinesin, TbKifX2C, was also found to associate with the MtQ. Simultaneous ablation of TbKifX2A and TbPH1 resulted in morphological defects and an expansion of the flagellar pocket. This study provides insights into the co-evolution of the X2 kinesin family and the MtQ in trypanosomatids.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biology
Matus Valach, Sandrine Moreira, Celine Petitjean, Corinna Benz, Anzhelika Butenko, Olga Flegontova, Anna Nenarokova, Galina Prokopchuk, Tom Batstone, Pascal Lapebie, Lionnel Lemogo, Matt Sarrasin, Paul Stretenowich, Pragya Tripathi, Euki Yazaki, Takeshi Nara, Bernard Henrissat, B. Franz Lang, Michael W. Gray, Tom A. Williams, Julius Lukes, Gertraud Burger
Summary: This study presents the first nuclear genome sequence from a diplonemid, revealing its genome size and structure. The analysis shows that the metabolic capacity of diplonemids underwent significant expansion, potentially through horizontal gene transfer. Furthermore, the study finds that diplonemids have predatory capabilities, playing an important role in degrading cell walls of various organisms as an energy source.
Article
Biochemistry & Molecular Biology
Matus Valach, Corinna Benz, Lisbeth C. Aguilar, Ondrej Gahura, Drahomira Faktorova, Alena Zikova, Marlene Oeffinger, Gertraud Burger, Michael W. Gray, Julius Lukes
Summary: The mitoribosome in diplonemids, the sister-group of kinetoplastids, is even more complex than previously thought. It has a mass of >5 MDa, contains as many as 130 integral proteins, and exhibits a high protein-to-RNA ratio of 11:1. This unusual composition reflects significant structural reduction of ribosomal RNAs, increased size of canonical mitoribosomal proteins, and presence of lineage-specific components, shedding light on the early assembly stages of mitoribosomes and the impact of evolutionary divergence.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Drahomira Faktorova, Kristina Zahonova, Corinna Benz, Joel B. Dacks, Mark C. Field, Julius Lukes
Summary: Sec13 plays multiple roles in different cellular processes as a component of COPII endoplasmic reticulum export vesicle coat, nuclear pore complex (NPC), and Seh1-associated (SEA)/GATOR nutrient-sensing complex. Euglenozoa possesses two Sec13 paralogues, with Sec13a interacting with COPII and NPC, and Sec13b interacting with Sec16 and SEA/GATOR complex. This suggests a distinct organization of coatomer complexes in euglenozoan flagellates.