ArticleScientific reports2017
RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- How colonization bottlenecks, tissue niches, and transmission strategies shape protozoan infections.Trends in parasitology · 2023Review
- Distinguishing functions of trypanosomatid protein kinases.Trends in parasitology · 2022Review
- Promastigote-to-Amastigote Conversion inPathogens (Basel, Switzerland) · 2022Review
- Structure, function and druggability of the African trypanosome flagellum.Journal of cellular physiology · 2022Review
- Forward Genetics in Apicomplexa Biology: The Host Side of the Story.Frontiers in cellular and infection microbiology · 2022Review
- Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host.PLoS neglected tropical diseases · 2021Article
- Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.Nature communications · 2021Article
- Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- Article
- Trypanosoma brucei ATR Links DNA Damage Signaling during Antigenic Variation with Regulation of RNA Polymerase I-Transcribed Surface Antigens.Cell reports · 2020Article
- Genetically Validated Drug Targets in Leishmania: Current Knowledge and Future Prospects.ACS infectious diseases · 2018Review
- RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.BMC genomics · 2018Article
- Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites.Frontiers in microbiology · 2018Review
- Article
- Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei.PLoS pathogens · 2017Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi. The presence of trypanosomes in the bloodstream was assessed using RNAi target sequencing (RITseq) and compared to growth in culture. We identified 49 PKs with a significant loss of fitness in vivo in two independent experiments, and a strong correlation between in vitro and in vivo loss of fitness for the majority. Nine PKs had a more pronounced growth defect in vivo, than in vitro. Amongst these PKs were several with putative functions related to stress responses mediated through the PI3K/TOR or MAPK signaling cascades, which act to protect the parasite from complement-mediated and osmotic lysis. Identification of these virulence-associated PKs provides new insights into T. brucei-host interaction and reveals novel potential protein kinase drug targets.
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