Plasmodium falciparum Merozoite Associated Armadillo Protein (PfMAAP) Is Apically Localized in Free Merozoites and Antibodies Are Associated With Reduced Risk of Malaria.

Yaw Aniweh,Evelyn Quansah,Essel Charles-Chess,Laty Gaye Thiam,Gathoni Kamuyu,Prince B Nyarko,Faith H A Osier,Kevin K A Tetteh,Gordon A Awandare,Kevin Marsh,David J Conway,Felix Ansah

doi:10.3389/fimmu.2020.00505

Abstract

Understanding the functional role of proteins expressed by Plasmodium falciparum is an important step toward unlocking potential targets for the development of therapeutic or diagnostic interventions. The armadillo (ARM) repeat protein superfamily is associated with varied functions across the eukaryotes. Therefore, it is important to understand the role of members of this protein family in Plasmodium biology. The Plasmodium falciparum armadillo repeats only (PfARO; Pf3D7_0414900) and P. falciparum merozoite organizing proteins (PfMOP; Pf3D7_0917000) are armadillo-repeat containing proteins previously characterized in P. falciparum. Here, we describe the characterization of another ARM repeat-containing protein in P. falciparum, which we have named the P. falciparum Merozoites-Associated Armadillo repeats protein (PfMAAP). Antibodies raised to three different synthetic peptides of PfMAAP show apical staining of free merozoites and those within the mature infected schizont. We also demonstrate that the antibodies raised to the PfMAAP peptides inhibited invasion of erythrocytes by merozoites from different parasite isolates. In addition, naturally acquired human antibodies to the N- and C- termini of PfMAAP are associated with a reduced risk of malaria in a prospective cohort analysis.

Highlights

Human malaria is caused by several species of the genus Plasmodium, with the majority of deaths attributed to Plasmodium falciparum
We describe the characterization of another member of the armadillo repeat family of proteins, encoded by gene locus PF3D7_1035900, which lies in an antigenic rich region of chromosome 10 among members of the msp3 gene family and several other antigen genes
We show that the recombinant proteins based on the N, central repeat and C- terminal regions are recognized by antibodies in plasma of malaria exposed individuals, with antibodies to the N and C- terminal conserved domains being associated with a lower prospective risk of contracting malaria

Summary

INTRODUCTION

Human malaria is caused by several species of the genus Plasmodium, with the majority of deaths attributed to Plasmodium falciparum. Notable invasionlinked protein families include the P. falciparum reticulocyte binding like protein homologs (PfRH1, 2a, 2b, 4, and 5) [3,4,5,6,7,8], the erythrocyte binding antigens (PfEBAs; EBA 140, 175, 181 & EBL1) [9,10,11,12,13,14] and the rhoptry neck proteins (RONs) [15, 16] Other proteins such as AMA1 [17] have been shown to play critical roles during the process of merozoite invasion. The armadillo repeat containing proteins are being characterized for their role during parasite development The importance of this protein family is highlighted by their involvement in fundamental processes essential to parasite biology, including but not restricted to gene regulation and cytokinesis. We show that the recombinant proteins based on the N-, central repeat and C- terminal regions are recognized by antibodies in plasma of malaria exposed individuals, with antibodies to the N and C- terminal conserved domains being associated with a lower prospective risk of contracting malaria

RESULTS

DISCUSSION

Ethics Statement

DATA AVAILABILITY STATEMENT