The repeat region of the circumsporozoite protein is critical for sporozoite formation and maturation in Plasmodium.

David J P Ferguson,Richard J Wall,Rita Tewari,Photini Sinnis,Pawan Malhotra,Alida Coppi,Amanda E Balaban,Benoit Poulin,Asif Mohmmed,Christine S Hopp,Eva-Maria Patzewitz,Olivier Silvie

doi:10.1371/journal.pone.0113923

Abstract

The circumsporozoite protein (CSP) is the major surface protein of the sporozoite stage of malaria parasites and has multiple functions as the parasite develops and then migrates from the mosquito midgut to the mammalian liver. The overall structure of CSP is conserved among Plasmodium species, consisting of a species-specific central tandem repeat region flanked by two conserved domains: the NH2-terminus and the thrombospondin repeat (TSR) at the COOH-terminus. Although the central repeat region is an immunodominant B-cell epitope and the basis of the only candidate malaria vaccine in Phase III clinical trials, little is known about its functional role(s). We used the rodent malaria model Plasmodium berghei to investigate the role of the CSP tandem repeat region during sporozoite development. Here we describe two mutant parasite lines, one lacking the tandem repeat region (ΔRep) and the other lacking the NH2-terminus as well as the repeat region (ΔNΔRep). We show that in both mutant lines oocyst formation is unaffected but sporozoite development is defective.

Highlights

Malaria is caused by apicomplexan protozoan parasites of the genus Plasmodium and is responsible for approximately 1 million deaths per year [1]
P. berghei ANKA parasites expressing GFP under the ef1alpha promoter (507cl1) were used as the parent clone for DRep mutant generation [24] and wild type P. berghei ANKA parasites were used for domain and the repeat region (DNDRep)
By immune-electron microscopy, circumsporozoite protein (CSP) is visible in oocysts by day 5 or 6 post blood meal, where it localizes to the oocyst plasma membrane and cytoplasm

Summary

Introduction

Malaria is caused by apicomplexan protozoan parasites of the genus Plasmodium and is responsible for approximately 1 million deaths per year [1]. As the mosquito probes for blood, sporozoites, the infective stage of the parasite, are injected into the skin of the mammalian host. Once in the blood stream, sporozoites reach the liver, where they arrest and invade hepatocytes after crossing the sinusoidal barrier. Inside hepatocytes they develop into exo-erythrocytic forms, which release merozoites to initiate blood stage infections [2]. The asexual blood stages are responsible for the clinical manifestations of the disease. A small proportion of asexual parasites develop into sexual stage gametocytes that are ingested with the blood upon mosquito feeding. Thousands of sporozoites develop in individual oocysts and when mature, egress into the hemocoel to invade the salivary glands and begin the cycle anew

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Results

Conclusion