A Plasmodium falciparum Host-Targeting Motif Functions in Export during Blood Stage Infection of the Rodent Malarial Parasite Plasmodium berghei

Julia J Mackenzie,Shaina Mann,Souvik Bhattacharjee,Kasturi Haldar,Noé D Gómez,Aric Gregson

doi:10.1371/journal.pone.0002405

Julia J Mackenzie, Shaina Mann + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0002405

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Journal: PloS one	Publication Date: Jun 11, 2008
Citations: 32	License type: CC BY 4.0

Affiliation: Northwestern University

Abstract

Plasmodium falciparum (P. falciparum) secretes hundreds of proteins—including major virulence proteins—into the host erythrocyte. In order to reach the host cytoplasm, most P. falciparum proteins contain an N terminal host-targeting (HT) motif composed of 11 amino acids. In silico analyses have suggested that the HT motif is conserved throughout the Plasmodium species but experimental evidence only exists for P. falciparum. Here, we show that in the rodent malaria parasite Plasmodium berghei (P. berghei) a reporter-like green fluorescent protein expressed by the parasite can be exported to the erythrocyte cytoplasm in a HT-specific manner. This provides the first experimental proof that the HT motif can function as a signal for protein delivery to the erythrocyte across Plasmodium species. Further, it suggests that P. berghei may serve as a model for validation of P. falciparum secretome proteins. We also show that tubovesicular membranes extend from the vacuolar parasite into the erythrocyte cytoplasm and speculate that these structures may facilitate protein export to the erythrocyte.

Highlights

Every year, several hundred million people are infected with P. falciparum, the cause of the most severe form of malaria in humans, and a significant fraction of infected individuals die from complications
Falciparum gene, PfHRPII, fused to a green fluorescence protein (GFP) [11,12] in a double crossover P. berghei replacement plasmid described in detail elsewhere, [13]
Mouse models of malaria are important tools for studying malarial pathogenesis, yet they are limited by the differences between the genomes of P. falciparum and rodent maglaria parasites (RMP) such as P. berghei

Summary

Introduction

Several hundred million people are infected with P. falciparum, the cause of the most severe form of malaria in humans, and a significant fraction of infected individuals die from complications. During blood-stage infection, the parasite resides in a parasitophorous vacuole (PV) within the erythrocyte, a cell devoid of organelles, protein synthesis and trafficking machinery. Within this unusual host cell, the parasite matures intracellularly and directs elaborate host cell remodeling, including development of various membranous structures within the erythrocyte cytoplasm and the protrusion of the erythrocyte surface into so-called knobs. These structural and antigenic changes are presumably required for both survival within the erythrocyte as well as avoidance of the host defenses [1]. P. falciparum erythrocyte membrane protein-1 (PfEMP1) and knob-associated histidine-rich protein (KAHRP) together form electron-dense protrusions on the surface of infected erythrocytes that are at least partially responsible for the highly virulent adhesive properties of P. falciparum [3,4,5]

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