Article
Multidisciplinary Sciences
Justin Y. Toh, Agathe Nkouawa, Saul Rojas Sanchez, Huafang Shi, Nikolay G. Kolev, Christian Tschudi
Summary: By targeting 86 transcripts through RNAi, 22 genes that positively or negatively regulate the progression towards infectivity in Trypanosoma brucei have been identified, including the previously unknown nucleic acid binding proteins CSD1 and CSD2. The study suggests a considerable overlap between the genes that regulate stumpy bloodstream form Trypanosoma and those that govern the development of metacyclic form parasites.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Joseph T. Smith Jr, Brianna Tylec, Arunasalam Naguleswaran, Isabel Roditi, Laurie K. Read
Summary: This study reveals the importance of mitochondrial mRNA editing in the developmental regulation of Trypanosoma brucei. The researchers found that temperature reduction and depletion of the differentiation-repressive kinase RDK1 can affect the metabolism of Trypanosoma brucei by altering the editing of mitochondrial cytochrome mRNAs.
Article
Microbiology
Christina Wilkinson, Meredith T. Morris
Summary: This study demonstrates a complex relationship between FBPase activity and extracellular glucose levels in Trypanosoma brucei, suggesting a potential additional role for FBPase in parasite metabolism. The differential expression of FBPase in various parasite cell lines and growth conditions implies regulation via post-translational modifications. These findings provide new insights into the metabolic pathways of Trypanosoma brucei.
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
Parasitology
Tania Bishola, Christine Clayton
Summary: In Trypanosoma brucei, ZC3H28 protein plays a vital role in stabilizing specific mRNAs and increasing protein levels. Mass spectrometry revealed that ZC3H28 is associated with ribosomal proteins, various RNA-binding proteins, and is involved in regulating long and poorly translated mRNAs.
Article
Biochemistry & Molecular Biology
Roberto Docampo, Anibal Eugenio Vercesi
Summary: This review discusses the mechanisms of mitochondrial oxidant generation and removal, and the involvement of Ca2+ in trypanosome cell death, highlighting the need for further studies on ROS generation, defense mechanisms, and mitochondrial permeability transition pore in trypanosomatids.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Parasitology
Kennedy W. Mwangi, Rosaline W. Macharia, Joel L. Bargul
Summary: The study constructed a gene co-expression network of insect-stage trypanosomes using RNA-Seq data and identified enriched modules for genes that play key roles in the parasite's development in the tsetse fly. Additionally, potential 3' UTR regulatory elements for genes in the same module were predicted using the FIRE tool. This network provides a valuable resource for identifying candidate genes for functional studies and understanding the molecular mechanisms underlying important biological processes during the parasite's development in the tsetse fly, which could lead to the identification of potential molecular targets for disease control.
PARASITES & VECTORS
(2021)
Review
Immunology
Nava Raj Poudyal, Kimberly S. Paul
Summary: This review discusses the availability and uptake mechanisms of fatty acids in Trypanosoma brucei. Fatty acids can be synthesized by the parasite or acquired from the host's surroundings. Fatty acids are crucial for the growth and survival of the parasite and are implicated in the survival of specific proteins. The relative contribution of parasite-derived and host-derived fatty acids to T. brucei biology and the molecular mechanisms of fatty acid uptake are still poorly understood.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Yan-Zi Wen, Hao-Tian Tang, Xiao-Li Cai, Na Wu, Jia-Zhen Xu, Bi-Xiu Su, Geoff Hide, Zhao-Rong Lun, De-Hua Lai
Summary: In this study, PAG3 was identified as a key nuclear gene involved in the slender to stumpy differentiation pathway of Trypanosoma brucei in the mammalian host. The loss of this gene might explain the inability of T. evansi and some T. equiperdum to differentiate and the adaptation to transmission cycles that bypass the tsetse vector or mechanical contact.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Manon Geerts, Nick Van Reet, Sander Leyten, Raf Berghmans, Kat S. Rock, Theresa H. T. Coetzer, Lauren E-A Eyssen, Philippe Buscher
Summary: The newly developed T. b. gambiense inhibition ELISA (g-iELISA) based on the principle of antibody binding showed high specificity and sensitivity, making it suitable for regional laboratories in gHAT endemic countries for monitoring and surveillance.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Kacper M. Sendra, Andrew K. Watson, Ekaterina Kozhevnikova, Anthony L. Moore, T. Martin Embley, Robert P. Hirt
Summary: This article investigates the role of highly reduced forms of mitochondria called mitosomes in parasites, revealing their importance in the progression of the parasite life cycle and the biosynthesis of essential proteins. Additionally, the authors demonstrate that T. hominis is a useful model for studying microsporidian parasites and testing therapeutic agents.
Review
Cell Biology
Bibo Li
Summary: Telomeres and subtelomeres play crucial roles in maintaining chromosome stability and adapting to environmental changes, particularly in the case of the Trypanosoma brucei parasite. The similarities and differences in telomere factors between T. brucei, human, and yeast cells are important for understanding genome stability mechanisms.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Microbiology
Emilia Jane McLaughlin, Karinna Rubio-Pena, Annick Dujeancourt-Henry, Lucy Glover
Summary: This study aimed to disrupt monoallelic VSG expression and found that the DNA sequence of the ectopic VSG is lost in a transcription-dependent manner following DSB-triggered VSG switching. The loss of the ectopic VSG does not disrupt the number or variety of templates used for BES DSB repair, revealing strict mechanisms within the cell to reinforce monoallelic expression during antigenic variation.
Article
Biochemistry & Molecular Biology
Samya S. Alenezi, Naif D. Alenezi, Godwin U. Ebiloma, Manal J. Natto, Marzuq A. Ungogo, John O. Igoli, Valerie A. Ferro, Alexander I. Gray, James Fearnley, Harry P. de Koning, David G. Watson
Summary: Propolis is a resin gathered by bees from plant exudates, and its composition depends on the nearby plants. It acts as an anti-infective and has anti-protozoal properties. Red Nigerian propolis was found to be highly active against Trypanosoma brucei and T. congolense, and four isoflavonoids isolated from the propolis displayed high activity against the parasites.
Article
Biochemistry & Molecular Biology
Tatiana Dias-Guerreiro, Joana Palma-Marques, Patricia Mourata-Goncalves, Graca Alexandre-Pires, Ana Valerio-Bolas, Aurea Gabriel, Telmo Nunes, Wilson Antunes, Isabel Pereira da Fonseca, Marcelo Sousa-Silva, Gabriela Santos-Gomes
Summary: The study showed that TbEVs can establish direct communication with cells of innate and adaptive immunity, influencing the differentiation and expansion of macrophages and T lymphocytes.
Article
Biochemistry & Molecular Biology
Isabella E. Maudlin, Steve Kelly, Angela Schwede, Mark Carrington
Summary: The bloodstream form of Trypanosoma brucei relies on antigenic variation of a cell surface coat composed of variant surface glycoprotein (VSG) for survival in mammalian hosts, with the integrity of the VSG coat being crucial for its persistence. Investigation into the regulation of VSG mRNA levels revealed that the copy number varies with the identity of the VSG and that a pathway detects synthesis of non-functional VSG protein, leading to an increase in VSG mRNA levels.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2021)
Article
Biology
Lori Peacock, Chris Kay, Chloe Farren, Mick Bailey, Mark Carrington, Wendy Gibson
Summary: The research reveals the existence of various cell types in meiotic stages among trypanosomes from tsetse salivary glands, suggesting the sequential production of haploid gametes through consecutive cell divisions.
COMMUNICATIONS BIOLOGY
(2021)
Article
Infectious Diseases
Julius Mulindwa, Geofrey Ssentamu, Enock Matovu, Kevin Kamanyi Marucha, Francisco Aresta-Branco, Claudia Helbig, Christine Clayton
Summary: Most researchers studying protist parasites use a limited number of laboratory-adapted isolates obtained decades ago, with little study on the effects of laboratory passages and in vitro culture adaptation. This study introduces two new strains of Trypanosoma brucei brucei, MAK65 and MAK98, showing changes in gene copy numbers during adaptation to culture. Trisomy and increased chromosome segments were observed in established cultured lines, providing useful strains for research on trypanosome differentiation and pathogenicity.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Parasitology
Tania Bishola, Christine Clayton
Summary: In Trypanosoma brucei, ZC3H28 protein plays a vital role in stabilizing specific mRNAs and increasing protein levels. Mass spectrometry revealed that ZC3H28 is associated with ribosomal proteins, various RNA-binding proteins, and is involved in regulating long and poorly translated mRNAs.
Article
Multidisciplinary Sciences
Franziska Falk, Kevin Kamanyi Marucha, Christine Clayton
Summary: Transcription in Trypanosoma brucei is mainly constitutive and polycistronic, relying on post-transcriptional mechanisms for gene expression control. EIF4E1 and 4EIP play crucial roles in regulating gene expression and parasite morphology transitions, while the relationship between TUT3 and 4EIP function remains unclear.
Article
Cell Biology
Carlos Cordon-Obras, Claudia Gomez-Linan, Sara Torres-Rusillo, Isabel Vidal-Cobo, Diana Lopez-Farfan, Alicia Barroso-del Jesus, Domingo Rojas-Barros, Mark Carrington, Miguel Navarro
Summary: This study reveals the transcription initiation mechanism of genes in trypanosomes, identifying sequence-specific promoters that regulate the transcription of protein-coding genes, and demonstrates the conservation of this promoter-mediated regulation in eukaryotes.
Article
Infectious Diseases
Tania Bishola Tshitenge, Lena Reichert, Bin Liu, Christine Clayton
Summary: This study demonstrates the developmental regulation of RBP10 and PGKC proteins in Trypanosoma brucei, which is essential for the parasite's growth and survival. The researchers identified six regulatory regions in the 3'-untranslated region of RBP10 mRNA and two independent regions in the 3'-untranslated region of PGKC mRNA that are responsible for developmental regulation. Despite the absence of obvious sequence similarities in these regulatory regions, trypanosome mRNAs have multiple regulatory sequences, potentially acting as a fail-safe mechanism to ensure correct regulation.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Tania Bishola Tshitenge, Christine Clayton
Summary: The RNA-binding protein DRBD18 in Trypanosoma brucei is involved in the export and processing of mRNA through binding to polypyrimidine tract motifs in the 3'-untranslated regions of mRNA precursors.
Article
Biology
Bin Liu, Christine Clayton
Summary: The study found that T. brucei RBP10 targets specific mRNAs for destruction and may be related to the UA(U)(6) motif. In vitro binding experiments showed that RBP10 does not distinguish between UA(U)(6) and UACUCUCU motifs.
BMC RESEARCH NOTES
(2022)
Article
Biochemistry & Molecular Biology
Franziska Falk, Rafael Melo Palhares, Albina Waithaka, Christine Clayton
Summary: In this study, the functions of different versions of the cap-binding translation initiation factor EIF4E in Trypanosoma brucei were investigated. It was found that EIF4E2 is associated with the RNA-binding protein SLBP2 in bloodstream forms, while EIF4E5 has no impact on growth and differentiation. Additionally, EIF4E2 is strongly associated with a subset of mRNAs that are maximally abundant in the S-phase, with their abundances decreased in EIF4E2 knock-out cells.
MOLECULAR MICROBIOLOGY
(2022)
Article
Infectious Diseases
Albina Waithaka, Olena Maiakovska, Dirk Grimm, Larissa Melo do Nascimento, Christine Clayton
Summary: This study describes a trans splicing reporter system that can be used for studying and screening the roles of sequences and proteins in mRNA processing. The results suggest that splice factor and SR-domain proteins may play key roles in splice site definition.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Biotechnology & Applied Microbiology
Amanda T. S. Albanaz, Mark Carrington, Alexander O. Frolov, Anna I. Ganyukova, Evgeny S. Gerasimov, Alexei Y. Kostygov, Julius Lukes, Marina N. Malysheva, Jan Votypka, Alexandra Zakharova, Kristina Zahonova, Sara L. Zimmer, Vyacheslav Yurchenko, Anzhelika Butenko
Summary: This study conducted genome sequencing and analysis on previously overlooked trypanosomatid species, revealing their genomic diversity and chromosomal variations. The findings provide a solid foundation for future research on the genetic basis of life cycle changes and adaptation to different hosts in this species.
Article
Parasitology
Alexander D. Cook, Mark Carrington, Matthew K. Higgins
Summary: This article reviews decades of evidence on the effect of complement on African trypanosomes, focusing on the discovery of a trypanosome receptor for complement C3. It critically assesses three recent studies that attempt to provide a structural and mechanistic view of how this receptor helps trypanosomes survive in the presence of complement.
TRENDS IN PARASITOLOGY
(2023)
Review
Microbiology
Anna Barcons-Simon, Mark Carrington, T. Nicolai Siegel
Summary: Antigenic variation is a strategy used by pathogens to evade the host immune system. This Review discusses the impact of nuclear organization on antigenic variation in protozoan parasites, specifically Trypanosoma brucei and Plasmodium falciparum. It highlights the relevance of nuclear organization in both mutually exclusive antigen expression and genome stability, which are essential for antigenic variation.
NATURE MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rupa Nagar, Isobel Hambleton, Michele Tinti, Mark Carrington, Michael A. J. Ferguson
Summary: In this study, the surface glycoconjugates of T. theileri were purified and partially characterized using biochemical and mass spectrometry-based approaches. It was found that the surface glycoconjugates consist of glycoproteins and glycolipids, including MSPs and TTPSPs. Furthermore, the glycolipids of T. theileri were shown to be larger and more diverse than those of its phylogenetic relative T. cruzi.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2023)