PfSPATR, a Plasmodium falciparum Protein Containing an Altered Thrombospondin Type I Repeat Domain Is Expressed at Several Stages of the Parasite Life Cycle and Is the Target of Inhibitory Antibodies

Abstract

The annotated sequence of chromosome 2 of Plasmodium falciparum was examined for genes encoding proteins that may be of interest for vaccine development. We describe here the characterization of a protein with an altered thrombospondin Type I repeat domain (PfSPATR) that is expressed in the sporozoite, asexual, and sexual erythrocytic stages of the parasite life cycle. Immunoelectron microscopy indicated that this protein was expressed on the surface of the sporozoites and around the rhoptries in the asexual erythrocytic stage. An Escherichia coli-produced recombinant form of the protein bound to HepG2 cells in a dose-dependent manner and antibodies raised against this protein blocked the invasion of sporozoites into a transformed hepatoma cell line. Sera from Ghanaian adults and from a volunteer who had been immunized with radiation-attenuated P. falciparum sporozoites specifically recognized the expression of this protein on transfected COS-7 cells. These data support the evaluation of this protein as a vaccine candidate.

A Conserved Molecular Motor Drives Cell Invasion and Gliding Motility across Malaria Life Cycle Stages and Other Apicomplexan Parasites

“…4B). Our identification of eight TRAP-related proteins excluded the recently identified secreted protein with altered thrombospondin repeat, PfS-PATR (40), that, despite having a modified TSR domain, does not have a definable transmembrane domain or a cytoplasmic tail.…”

“…Orthologues-The TSR sequence of TRAP (PlasmoDB ID: PF13_0201 (12)) and CTRP (PFC0640w (13)) were used as BLASTP and TBLASTN queries to search the P. falciparum genome (24) 8,16,24,32,40, and 48 h postinvasion using TRIzol (Invitrogen). RNA was further purified using DNase I digestion by passage over an RNAeasy column (Qiagen) to remove any residual genomic DNA.…”

A long and winding road: The Plasmodium sporozoite's journey in the mammalian host

“…They function during merozoite invasion of erythrocytes [78,79] and antibody inhibition studies show that they are also involved in sporozoite invasion of hepatocytes [80]. Other proteins for which a role in hepatocyte invasion is suggested either by their localization in the sporozoite or the fact that antibodies directed against them can decrease sporozoite infectivity include SPATR [81], EBA 175 [82], STARP [83] and PfEMP3 [84].…”

Annotation transfer by homology among closely related genomes helps to identify protein function in Plasmodium species

“…The SPATR protein (XP_001349632.1) 1 which contains an altered thrombospondin type I repeat domain is found expressed at several stages of the parasitic life cycle. The blocking of this protein inhibits the infection of the parasite and it has been proposed as a vaccine candidate (Chattopadhyay et al, 2003). Heat shock proteins (XP_001351159.1) in Plasmodium have a role in invasion of the host and have attracted attention as drug targets (Shonhai, 2010).…”