Baker, N, Catta-Preta, C M C, Neish, R et al. (15 more authors) (2021) Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival. Nature Communications. 1244. ISSN 2041-1723
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2021 |
Keywords: | Animals,CRISPR-Associated Protein 9/metabolism,CRISPR-Cas Systems/genetics,Cell Differentiation,Cell Survival,Female,Flagella/enzymology,Gene Deletion,Leishmania mexicana/cytology,Leishmaniasis/parasitology,Mice, Inbred BALB C,Models, Biological,Mutation/genetics,Protein Kinases/genetics,Proteome/metabolism,Psychodidae/parasitology |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Physics (York) The University of York > Research Groups (York) > Centre for Medieval Studies (York) The University of York > Faculty of Arts and Humanities (York) > Music (York) The University of York > Faculty of Sciences (York) > Environment and Geography (York) The University of York > Faculty of Sciences (York) > Mathematics (York) |
Depositing User: | Pure (York) |
Date Deposited: | 24 Feb 2021 16:20 |
Last Modified: | 13 Mar 2025 05:27 |
Published Version: | https://doi.org/10.1038/s41467-021-21360-8 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-021-21360-8 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171554 |