Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.

Autor: Baker N; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Catta-Preta CMC; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Neish R; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Sadlova J; Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic., Powell B; Department of Mathematics, University of York, York, UK., Alves-Ferreira EVC; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Geoghegan V; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Carnielli JBT; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Newling K; Department of Biology, University of York, York, UK., Hughes C; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Vojtkova B; Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic., Anand J; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Mihut A; Department of Biology, University of York, York, UK., Walrad PB; York Biomedical Research Institute, University of York, York, UK.; Department of Biology, University of York, York, UK., Wilson LG; York Biomedical Research Institute, University of York, York, UK.; Department of Physics, University of York, York, UK., Pitchford JW; Department of Biology, University of York, York, UK.; Department of Mathematics, University of York, York, UK., Volf P; Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic., Mottram JC; York Biomedical Research Institute, University of York, York, UK. jeremy.mottram@york.ac.uk.; Department of Biology, University of York, York, UK. jeremy.mottram@york.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Feb 23; Vol. 12 (1), pp. 1244. Date of Electronic Publication: 2021 Feb 23.
DOI: 10.1038/s41467-021-21360-8
Abstrakt: Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and for transmission between hosts, requiring stringent spatial and temporal regulation. Here, we apply kinome-wide gene deletion and gene tagging in Leishmania mexicana promastigotes to define protein kinases with life cycle transition roles. Whilst 162 are dispensable, 44 protein kinase genes are refractory to deletion in promastigotes and are likely core genes required for parasite replication. Phenotyping of pooled gene deletion mutants using bar-seq and projection pursuit clustering reveal functional phenotypic groups of protein kinases involved in differentiation from metacyclic promastigote to amastigote, growth and survival in macrophages and mice, colonisation of the sand fly and motility. This unbiased interrogation of protein kinase function in Leishmania allows targeted investigation of organelle-associated signalling pathways required for successful intracellular parasitism.
Databáze: MEDLINE
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