The malaria parasite Plasmodium falciparum in red blood cells selectively takes up serum proteins that affect host pathogenicity

Takahiro Tougan,Eizo Takashima,Toshihiro Horii,Takafumi Tsuboi,Hajime Honma,Jyotheeswara R. Edula,Masayuki Morita

doi:10.1186/s12936-020-03229-1

Abstract

BackgroundThe malaria parasite Plasmodium falciparum is a protozoan that develops in red blood cells (RBCs) and requires various host factors. For its development in RBCs, nutrients not only from the RBC cytosol but also from the extracellular milieu must be acquired. Although the utilization of host nutrients by P. falciparum has been extensively analysed, only a few studies have reported its utilization of host serum proteins. Hence, the aim of the current study was to comprehensively identify host serum proteins taken up by P. falciparum parasites and to elucidate their role in pathogenesis.MethodsPlasmodium falciparum was cultured with human serum in vitro. Uptake of serum proteins by parasites was comprehensively determined via shotgun liquid chromatography–mass spectrometry/mass spectrometry and western blotting. The calcium ion concentration in serum was also evaluated, and coagulation activity of the parasite lysate was assessed.ResultsThree proteins, vitamin K-dependent protein S, prothrombin, and vitronectin, were selectively internalized under sufficient Ca2+ levels in the culture medium. The uptake of these proteins was initiated before DNA replication, and increased during the trophozoite and schizont stages, irrespective of the assembly/disassembly of actin filaments. Coagulation assay revealed that prothrombin was activated and thereby induced blood coagulation.ConclusionsSerum proteins were taken up by parasites under culture conditions with sufficient Ca2+ levels. This uptake phenomenon was associated with their pathogenicity.

Highlights

The malaria parasite Plasmodium falciparum is a protozoan that develops in red blood cells (RBCs) and requires various host factors
Serum proteins are selectively taken up into iRBCs by P. falciparum parasites The total protein in plasma-derived serum (PDS), and within intact parasites in iRBCs cultured in Plasma-derived serum (PDS)-containing culture medium was analysed by shotgun LC– MS/MS analysis
The uptake ratio of vitronectin was relatively low (3.99; Table 1) it was internalized in a strongly selective manner (Fig. 1a), as previously reported [8]. These findings suggest that serum proteins were selectively taken up, rather than diffusing into iRBCs

Summary

Introduction

The malaria parasite Plasmodium falciparum is a protozoan that develops in red blood cells (RBCs) and requires various host factors. The aim of the current study was to comprehensively identify host serum proteins taken up by P. falciparum parasites and to elucidate their role in pathogenesis. The malaria parasite Plasmodium falciparum is a protozoan that reproduces in red blood cells (RBCs) and requires various host factors for its development and survival. Cytoplasmic C a2+ concentration has been shown to slowly increase during parasite development, activating both host and parasite proteases during the schizont stage, and inducing merozoite egress from iRBCs [13,14,15]. Activation of blood coagulation is frequently observed in patients with malaria, which subsequently induces inflammation and severe malaria-associated symptoms. IRBC adhesion dramatically decreases, and adherent iRBCs detach [20]

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