Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression

Carnielli JBT, Brannigan JA, Ramos PZ, Jones NG, Couñago RM, Sjö P, Lima APCA, Wilkinson AJ, Mottram JC. PLOS Pathogens 2026,22(5): e1014194. doi.org/10.1371/journal.ppat.1014194

Summary: Protein kinases are key regulators of the eukaryotic cell cycle and have emerged as attractive targets for drug development. The Leishmania kinome, shaped by diverse evolutionary processes, harbours a unique repertoire of potential drug targets.
The authors of this manuscript investigated the presence of reactive cysteine residues within the Leishmania kinome and identified five essential protein kinases containing cysteine residues amenable to covalent modification. Using CRISPR-Cas9 to genetically modify L. mexicana protein kinases, analog-sensitive kinase mutants were generated to investigate their essential functions. Two kinases were found to be indispensable for survival in the form that infects humans. These findings highlight new potential drug targets and provide a chemical genetics platform for studying how essential protein kinases function in Leishmania.

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