Baculovirus-expressed Plasmodium reichenowi EBA-140 merozoite ligand is host specific

Zerka, Agata; Olechwier, Agnieszka; Rydzak, Joanna; Kaczmarek, Radosław; Jaśkiewicz, Ewa

doi:10.1016/j.parint.2016.07.009

Cited by 5 publications

(5 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To identify it, we used a soluble, recombinant Region II obtained in insect cells. We showed previously that the P. reichenowi Region II of EBA-140 binds specifically to chimpanzee erythrocytes in a sialic acid-dependent manner [ 44 ]. We found that binding of the EBA-140 Region II to GPD is markedly decreased by treatment of erythrocytes with chymotrypsin.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plasmodium reichenowi EBA-140 merozoite ligand binds to glycophorin D on chimpanzee red blood cells, shedding new light on origins of Plasmodium falciparum

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundAll symptoms of malaria are caused by the intraerythrocytic proliferation of Plasmodium merozoites. Merozoites invade erythrocytes using multiple binding ligands that recognise specific surface receptors. It has been suggested that adaptation of Plasmodium parasites to infect specific hosts is driven by changes in genes encoding Plasmodium erythrocyte-binding ligands (EBL) and reticulocyte-binding ligands (RBL). Homologs of both EBL and RBL, including the EBA-140 merozoite ligand, have been identified in P. falciparum and P. reichenowi, which infect humans and chimpanzees, respectively. The P. falciparum EBA-140 was shown to bind human glycophorin C, a minor erythrocyte sialoglycoprotein. Until now, the erythrocyte receptor for the P. reichenowi EBA-140 remained unknown.MethodsThe baculovirus expression vector system was used to obtain the recombinant EBA-140 Region II, and flow cytometry and immunoblotting methods were applied to characterise its specificity.ResultsWe showed that the chimpanzee glycophorin D is the receptor for the P. reichenowi EBA-140 ligand on chimpanzee red blood cells.ConclusionsWe propose that the development of glycophorin C specificity is spurred by the P. falciparum lineage. We speculate that the P. falciparum EBA-140 evolved to hijack GPC on human erythrocytes during divergence from its ape ancestor.

show abstract

Section: Discussionmentioning

confidence: 99%

“…To explain the role of GPC and GPD in P. reichenowi binding, we used the recombinant binding region (Region II) of P. reichenowi EBA-140 obtained in baculovirus expression vector system [ 44 ]. We demonstrate that the receptor for the P. reichenowi EBA-140 is probably the homolog of human glycophorin D on chimpanzee erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium reichenowi EBA-140 merozoite ligand binds to glycophorin D on chimpanzee red blood cells, shedding new light on origins of Plasmodium falciparum

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…reichenowi . We have shown that the recombinant ape EBA-140 RII specifically recognizes sialylated oligosaccharides on chimpanzee RBCs [ 59 ]. The glycophorin D (a truncated form of GPC) was identified as receptor for P .…”

Section: Sialic Acidsmentioning

confidence: 99%

Red Blood Cells Oligosaccharides as Targets for Plasmodium Invasion

et al. 2022

Self Cite

View full text Add to dashboard Cite

The key element in developing a successful malaria treatment is a good understanding of molecular mechanisms engaged in human host infection. It is assumed that oligosaccharides play a significant role in Plasmodium parasites binding to RBCs at different steps of host infection. The formation of a tight junction between EBL merozoite ligands and glycophorin receptors is the crucial interaction in ensuring merozoite entry into RBCs. It was proposed that sialic acid residues of O/N-linked glycans form clusters on a human glycophorins polypeptide chain, which facilitates the binding. Therefore, specific carbohydrate drugs have been suggested as possible malaria treatments. It was shown that the sugar moieties of N-acetylneuraminyl-N-acetate-lactosamine and 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA), which is its structural analog, can inhibit P. falciparum EBA-175-GPA interaction. Moreover, heparin-like molecules might be used as antimalarial drugs with some modifications to overcome their anticoagulant properties. Assuming that the principal interactions of Plasmodium merozoites and host cells are mediated by carbohydrates or glycan moieties, glycobiology-based approaches may lead to new malaria therapeutic targets.

show abstract

“…The EBA-175 (175-kDa) protein belongs to the erythrocyte binding protein (EBP) family, which enables Mrz to interact with RBC and whose presence or absence defines alternative invasion routes (Zerka et al, 2016). The EBA-175 structure is formed by eight regions: a transmembrane one, a cytoplasmic one, and six extracellular regions or domains (I–VI).…”

Section: Clinical Studies Regarding Blood-stage Malaria Vaccinesmentioning

confidence: 99%

Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines

et al. 2019

View full text Add to dashboard Cite

Plasmodium falciparum malaria is a disease causing high morbidity and mortality rates worldwide, mainly in sub-Saharan Africa. Candidates have been identified for vaccines targeting the parasite’s blood stage; this stage is important in the development of symptoms and clinical complications. However, no vaccine that can directly affect morbidity and mortality rates is currently available. This review analyzes the formulation, methodological design, and results of active clinical trials for merozoite-stage vaccines, regarding their safety profile, immunological response (phase Ia/Ib), and protective efficacy levels (phase II). Most vaccine candidates are in phase I trials and have had an acceptable safety profile. GMZ2 has made the greatest progress in clinical trials; its efficacy has been 14% in children aged less than 5 years in a phase IIb trial. Most of the available candidates that have shown strong immunogenicity and that have been tested for their protective efficacy have provided good results when challenged with a homologous parasite strain; however, their efficacy has dropped when they have been exposed to a heterologous strain. In view of these vaccines’ unpromising results, an alternative approach for selecting new candidates is needed; such line of work should be focused on how to increase an immune response induced against the highly conserved (i.e., common to all strains), functionally relevant, protein regions that the parasite uses to invade target cells. Despite binding regions tending to be conserved, they are usually poorly antigenic and/or immunogenic, being frequently discarded as vaccine candidates when the conventional immunological approach is followed. The Fundación Instituto de Inmunología de Colombia (FIDIC) has developed a logical and rational methodology based on including conserved high-activity binding peptides (cHABPs) from the main P. falciparum biologically functional proteins involved in red blood cell (RBC) invasion. Once appropriately modified (mHABPs), these minimal, subunit-based, chemically synthesized peptides can be used in a system covering the human immune system’s main genetic variables (the human leukocyte antigen HLA-DR isotype) inducing a suitable, immunogenic, and protective immune response in most of the world’s populations.

show abstract

Baculovirus-expressed Plasmodium reichenowi EBA-140 merozoite ligand is host specific

Cited by 5 publications

References 52 publications

Plasmodium reichenowi EBA-140 merozoite ligand binds to glycophorin D on chimpanzee red blood cells, shedding new light on origins of Plasmodium falciparum

Plasmodium reichenowi EBA-140 merozoite ligand binds to glycophorin D on chimpanzee red blood cells, shedding new light on origins of Plasmodium falciparum

Red Blood Cells Oligosaccharides as Targets for Plasmodium Invasion

Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines

Contact Info

Product

Resources

About