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.
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
Entomology
Zhiyuan Yang, Mai Shi, Xiaoli Zhang, Danyu Yao
Summary: This study dissected the genomic and transcriptomic profiles of T. brucei, identifying a panel of pathogenic proteins and microRNAs. The findings contribute to a better understanding of the parasite-host interaction mechanisms and provide new insights for designing preventive and therapeutic strategies for African trypanosomiasis.
Article
Immunology
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
Summary: The study investigates the cyclic AMP (cAMP) signaling in trypanosomes and reveals the difference in cAMP pathways compared to other eukaryotes. Through genome-wide RNAi screening, four genes named cAMP Response Protein (CARP) 1-4 were identified as related to resistance to the cAMP phosphodiesterase inhibitor NPD-001. Additionally, six CARP candidate genes were discovered through deep sequencing, and their resistance phenotypes were confirmed. The study highlights the significance of cAMP in flagellar function and provides a resource for exploring unusual cAMP pathways and flagellar biology.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Parasitology
Sara Silva Pereira, Kawira Mathenge, Daniel Masiga, Andrew Jackson
Summary: This study conducted transcriptome analysis of trypanosome parasites from naturally infected tsetse flies and found a phylotype 8 variant surface glycoprotein (VSG) gene to be constitutively expressed in metacyclic- and bloodstream-form parasites.
PARASITES & VECTORS
(2022)
Article
Entomology
Xiangzhao Yue, Yongkang Liang, Zhishuang Wei, Jun Lv, Yongjin Cai, Xiaobin Fan, Wenqing Zhang, Jie Chen
Summary: This study identified potential kkv transcriptional regulators through comprehensive RNA interference analyses and validated their roles in vivo using transgenic Drosophila lines. Fer3 was shown to be crucial for activating kkv transcription and regulating genes involved in chitin synthesis. The study also revealed a potential complex mechanism of kkv transcription regulation involving an interaction network with bithorax complex components.
Article
Microbiology
Gustavo Bravo Ruiz, Michele Tinti, Melanie Ridgway, David Horn
Summary: VSG expression plays a crucial role in parasite virulence and is a fascinating subject in extreme biology. This study identified three candidate VSG regulators and demonstrated the role of CFB2 in controlling VSG expression through the VSG 3' UTR. Additionally, insights into the connections between VSG expression control, ribosomal protein expression, and cytokinesis were revealed.
Article
Biochemistry & Molecular Biology
Kamini Kaushal, Eun-Jung Kim, Apoorvi Tyagi, Janardhan Keshav Karapurkar, Saba Haq, Han-Sung Jung, Kye-Seong Kim, Suresh Ramakrishna
Summary: The deubiquitinating enzyme USP49 interacts with and stabilizes the protein levels of PAX9 and MSX1, promoting successful tooth development.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Dagmar Flittner, Marcel Kaiser, Pascal Maeser, Norberto P. Lopes, Thomas J. Schmidt
Summary: Research found that Pachysandra terminalis contains amino steroids with anti-trypanosomal activity, with activity-guided fractionation and mass spectrometry analysis identifying 18 constituents responsible for this activity.
Article
Microbiology
Kirsten J. Meyer, Theresa A. Shapiro
Summary: The study found that Hsp90 plays a central role as molecular chaperones in African trypanosomes, with unique functions in cell cycle regulation and kinetoplast DNA replication revealed through knockdown of cytosolic and mitochondrial Hsp90s.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Ying Hu, Xin Li, Jing Zhang, Dengfeng Liu, Renbin Lu, Jia-Da Li
Summary: This study identifies deubiquitinase USP1 as a previously unknown regulator of the mammalian circadian clock and highlights the potential of genome-wide CRISPR screens in the identification of regulators for the circadian clock.
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
Genetics & Heredity
Delesa Damena, Francis E. Agamah, Peter O. Kimathi, Ntumba E. Kabongo, Hundaol Girma, Wonderful T. Choga, Lemu Golassa, Emile R. Chimusa
Summary: Recent GWAS studies identified several association variants with severe malaria, but much remains unknown about the biological functions. This study systematically predicted candidate genes and pathways involved in severe malaria resistance, revealing multiple genes enriched in pathogenic pathways and higher minor allele frequencies in endemic populations compared to global populations. These findings suggest the potential for new malaria therapeutics targeting multiple protective host molecular pathways.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Jianting Shi, Xun Wu, Ziyi Wang, Fang Li, Yujiao Meng, Rebecca M. Moore, Jian Cui, Chenyi Xue, Katherine R. Croce, Arif Yurdagul, John G. Doench, Wei Li, Konstantinos S. Zarbalis, Ira Tabas, Ai Yamamoto, Hanrui Zhang
Summary: This study identified WDFY3 as a novel regulator of efferocytosis through a genome-wide CRISPR screen, revealing its role in promoting LC3 lipidation and lysosomal acidification for the degradation of apoptotic cell components.
NATURE COMMUNICATIONS
(2022)
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
Biology
Frank Venter, Keith R. Matthews, Eleanor Silvester
Summary: Laboratory studies of pathogens often overlook the interactions between pathogens and hosts, despite the fact that hosts frequently sustain co-infections with multiple pathogens. These interactions between co-infecting pathogens and the host immune system are complex and can greatly affect disease outcomes. Researchers have used ecological and experimental studies of trypanosome and malaria infections to examine these interactions.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Review
Parasitology
David Horn
Summary: Genome-scale genetic screens have played a crucial role in African trypanosomes by uncovering mechanisms related to drug resistance, metabolism, and gene expression control. They have also been effective in identifying potential antitrypanosomal drug targets.
TRENDS IN PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simone Altmann, Eva Rico, Sandra Carvalho, Melanie Ridgway, Anna Trenaman, Hannah Donnelly, Michele Tinti, Susan Wyllie, David Horn
Summary: This study reports a simple method for rapid and precise editing of priority drug targets in trypanosomatids. By targeting and editing drug targets, combined with sequencing technology, potential impacts on drug efficacy can be assessed quickly.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Guy R. Oldrieve, Beatrice Malacart, Javier Lopez-Vidal, Keith R. Matthews
Summary: This study explores the host and vector specificity between Trypanosoma theileri and Trypanosoma melophagium, non-pathogenic parasites of bovines and sheep, respectively. The contrasting genomic features of these species are likely associated with their mode of transmission from their insect vector to their mammalian host.
Article
Microbiology
Gustavo Bravo Ruiz, Michele Tinti, Melanie Ridgway, David Horn
Summary: VSG expression plays a crucial role in parasite virulence and is a fascinating subject in extreme biology. This study identified three candidate VSG regulators and demonstrated the role of CFB2 in controlling VSG expression through the VSG 3' UTR. Additionally, insights into the connections between VSG expression control, ribosomal protein expression, and cytokinesis were revealed.
Article
Multidisciplinary Sciences
Mabel Deladem Tettey, Federico Rojas, Keith R. Matthews
Summary: This study identifies secreted peptidases released by trypanosomes and systematically assesses their role in stumpy formation in vivo. The results demonstrate the dominance of oligopeptidase B and metallocarboxypeptidase 1 in quorum sensing.
NATURE COMMUNICATIONS
(2022)
Correction
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
NATURE REVIEWS MICROBIOLOGY
(2022)
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are major causes of death and illness, particularly in low- and middle-income countries. The development of new medicines for leishmaniasis and Chagas disease is urgently needed, with limited progress in the clinical pipeline for Chagas disease. This review provides an overview of recent advances in understanding the biology of these pathogens, with a focus on drug discovery, as well as the development of new drug candidates and potential solutions to overcome challenges in clinical development.
NATURE REVIEWS MICROBIOLOGY
(2023)
Review
Parasitology
Mathieu Cayla, Y. Romina Nievas, Keith R. Matthews, Jeremy C. Mottram
Summary: Trypanosomatid parasitic protozoa have evolved unique mechanisms, such as protein kinases, to regulate their complex life cycles and adapt to different hosts, distinguishing them from other eukaryotes.
TRENDS IN PARASITOLOGY
(2022)
Article
Multidisciplinary Sciences
Catarina A. Marques, Melanie Ridgway, Michele Tinti, Andrew Cassidy, David Horn
Summary: In this study, a genome-wide RNA-interference library screen was used to investigate the cell cycle defects in Trypanosoma brucei. The results provide comprehensive functional genomic evidence for the known and novel machineries, pathways, and regulators that coordinate trypanosome cell cycle progression.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Desislava P. Staneva, Stefan Bresson, Tatsiana Auchynnikava, Christos Spanos, Juri Rappsilber, A. Arockia Jeyaprakash, David Tollervey, Keith R. Matthews, Robin C. Allshire
Summary: This study reveals the unique gene expression regulation mechanism in kinetoplastids, a highly divergent lineage of eukaryotes. The researchers identified a complex called SPARC, which consists of SET27 and CRD1, among other components, that is involved in establishing accurate promoter position and directionality.
Review
Immunology
Liam J. J. Morrison, Pieter C. C. Steketee, Mabel D. D. Tettey, Keith R. R. Matthews
Summary: African trypanosomes are protozoa that are transmitted by vectors and cause significant disease in humans and animals. The severity of infection varies depending on the species of Trypanosoma and the host, making intervention design challenging. This review provides an overview of the current understanding of trypanosome determinants of infection progression and severity, highlighting knowledge gaps and opportunities for developing novel interventions.
Article
Microbiology
Douglas Escrivani, Viktor Scheidt, Michele Tinti, Joana Faria, David Horn
Summary: Some pathogens use antigenic variation to evade mammalian host adaptive immune responses. African trypanosomes employ variant surface glycoproteins (VSGs) to continually switch their active VSGs and avoid immune recognition. Switched trypanosomes compete in a predictable manner that is dependent on the activated VSG, and the population of cells that activates minichromosome derived VSGs has a competitive advantage.
Article
Microbiology
Anna Trenaman, Michele Tinti, Abdelmadjid Atrih, David Horn
Summary: Nucleoside analogs are widely used as anti-infective agents, but their potential as anti-parasitic agents has not been fully explored. This study identified two proteins, Tb927.6.2800 and HD82, associated with purine analog resistance in African trypanosomes. The findings also validated two nucleoside kinases involved in pro-drug activation. HD82, related to the mammalian nuclear viral restriction factor SAMHD1, sensitized trypanosomes to nucleoside analogs by reducing native nucleotide pools. This study provides insights into nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.
Review
Microbiology
Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert
Summary: Leishmaniasis, Chagas disease, and human African trypanosomiasis are causing significant death and morbidity, especially in low- and middle-income countries. There is a critical need for new medications for leishmaniasis and Chagas disease, while the clinical development pipeline for Chagas disease remains sparse. This review discusses recent advancements in understanding the biology of these pathogens, with a focus on drug discovery, and explores progress in developing new drug candidates and identifying potential molecular targets. The challenges in developing new clinical candidates are also discussed, along with potential solutions to overcome these hurdles.
NATURE REVIEWS MICROBIOLOGY
(2023)
