Functional Characterization of Plasmodium Falciparum Claudin-Like Apicomplexan Microneme Protein (Pfclamp) (Pf3d7_1030200)

Abstract

Malaria is still a public health burden. With the recent reports of artemisinin resistance in Plasmodium falciparum coupled with the low efficacy of the RTS, S vaccine currently under a WHO-recommended pilot malaria vaccine implementation programme (MVIP), there is the need to continue identifying new targets by functionally characterizing some of the ~60% of the parasite’s genes with unknown functions. This will foster the identification of viable vaccine and possible drug targets for the development of interventions against the parasite. This project focused on studying P. falciparum Claudin-Like Apicomplexan Microneme Protein (PfCLAMP) with gene ID (Pf3D7_1030200) and its role during invasion of the parasite. CLAMP has been shown to be highly conserved in apicomplexans, with its orthologue in P. falciparum being essential for parasite growth and invasion. Here, using specific antibodies raised against the extracellular domain of the PfCLAMP, we report that PfCLAMP localizes at the apical portion of merozoites. The generated antibodies inhibited parasite invasion in a dose dependent manner. We have also observed that PfCLAMP is differentially expressed across the different asexual stages of the parasite, with peak expression occurring at the late stages of the parasite. We also discovered that some clinical isolates habour multiple copies of the PfCLAMP gene. Additionally, we show that PfCLAMP conditional gene knockout reduced invasion by up to 30% in the first cycle of the parasite development. Altogether, our data demonstrates that PfCLAMP provides a potentially attractive target for further investigation for drug and vaccine development.