Abstract

Plasmodium Calcium Dependent Protein Kinase (CDPK1) is required for the development of sexual stages in the mosquito. In addition, it is proposed to play an essential role in the parasite’s invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. We demonstrate that Plasmodium berghei CDPK1 is dispensable in the parasite’s erythrocytic and pre-erythrocytic stages. We successfully disrupted P. berghei CDPK1 (PbCDPK1) by homologous recombination. The recovery of erythrocytic stage parasites lacking PbCDPK1 (PbCDPK1-) demonstrated that PbCDPK1 is not essential for erythrocytic invasion or intra-erythrocytic development. To study PbCDPK1’s role in sporozoites and liver stage parasites, we generated a conditional mutant (CDPK1 cKO). Phenotypic characterization of CDPK1 cKO sporozoites demonstrated that CDPK1 is redundant or dispensable for the invasion of mammalian hepatocytes, the egress of parasites from infected hepatocytes and through the subsequent erythrocytic cycle. We conclude that P. berghei CDPK1 plays an essential role only in the mosquito sexual stages.

Highlights

  • Ca2+ signaling plays a crucial role in Apicomplexan parasites

  • A major mediator of Ca2+ signaling in Apicomplexans is a family of Calcium Dependent Protein Kinases (CDPK) that is unique to Apicomplexans, plants and some algae

  • It is expressed through out the parasite lifecycle [16,17] suggesting that it has multiple roles in different parasite stages. It is best studied in Plasmodium berghei sexual stages, where CDPK1 controls the transcription of a subset of translationally-repressed mRNAs, and a knock down of P. berghei CDPK1 (PbCDPK1) blocks ookinete development [16]

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Summary

Introduction

Ca2+ signaling plays a crucial role in Apicomplexan parasites. It mediates micronemal protein secretion in Plasmodium [1], Toxoplasma [2,3,4], Cryptosporodium [5] and Eimeria [6]. The recovery of parasites lacking CDPK1 demonstrates that PbCDPK1 is not essential during the erythrocytic cycle. To determine if lack of PbCDPK1 compromises intra-erythrocytic development in the parasite, we monitored the growth rate of CDPK1- erythrocytic stages in mice (Fig. 1D). CDPK1 is not Essential in Pre-erythrocytic Stages PbCDPK1 and one of its putative substrates, MTIP are present in sporozoites [16].

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