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

N Baker, C M C Catta-Preta, R Neish, J Sadlova, B Powell, E V C Alves-Ferreira, V Geoghegan, J B T Carnielli, K Newling, C Hughes, B Vojtkova, J Anand, A Mihut, P B Walrad, L G Wilson, J W Pitchford, P Volf, J C Mottram

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1244
Number of pages15
JournalNature Communications
Issue number1
Early online date23 Feb 2021
Publication statusPublished - 23 Feb 2021

Bibliographical note

© The Author(s) 2021


  • 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

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