A putative serine-threonine kinase 2 () is required for late liver stage development and timely initiation of blood stage infection.

In , protein kinases govern key biological processes of the parasite life cycle involved in the establishment of infection, dissemination and sexual reproduction. The rodent malaria model encodes for 66 putative eukaryotic protein kinases (ePKs) as identified through modelling domain signatures and are highly conserved in We report here the functional characterisation of a putative serine-threonine kinase identified in this kinome analysis and designate it as To elucidate its role, we knocked out locus and performed a detailed phenotypic analysis at different life cycle stages. The knockout (KO) was not compromised in asexual blood stage propagation, transmission and development in the mosquito vector. The KO produced viable salivary gland sporozoites that successfully transformed into exo-erythrocytic forms (EEFs) and were morphologically indistinguishable from wild-type GFP (WT GFP) with regard to size and shape until 48 h. An intravenous dose of 1×10 KO sporozoites in C57BL/6 mice failed to establish blood stage infection and a higher dose of 5X10 showed a 2-3 day delay in prepatency as compared to WT GFP parasites. Consistent with such an observation, analysis of EEF development at 62 h revealed that the hepatic merozoite numbers were reduced to nearly 40% as compared to WT GFP and showed meagre expression of MSP1. Our studies provide evidence for the role of STK2 in late liver stage development and for the successful establishment of a timely blood stage infection.