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Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood-brain barrier in cerebral malaria

March 2, 2021 - 15:15 -- Open Access
Adams Y, Olsen RW, Jensen ATR, et al.
J Exp Med. 2021 Mar 1;218(3):e20201266

Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum-infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling. We have previously linked dual intercellular adhesion molecule-1 (ICAM-1)- and endothelial protein C receptor (EPCR)-binding P. falciparum parasites to these symptoms, but the mechanism driving the pathogenesis has not been identified.

NOT Open Access | A prospective mechanism and source of cholesterol uptake by Plasmodium falciparum-infected erythrocytes co-cultured with HepG2 cells

February 3, 2021 - 14:57 -- NOT Open Access
Hayakawa EH, Kato H, Nardone GA, Usukura J
Parasitol Int. 2021 Feb;80:102179

Plasmodium falciparum (P. falciparum) parasites still cause lethal infections worldwide, especially in Africa ( During P. falciparum blood-stage infections in humans, low-density lipoprotein, high-density lipoprotein and cholesterol levels in the blood become low. Because P. falciparum lacks a de novo cholesterol synthesis pathway, it must import cholesterol from the surrounding environment. However, the origin of the cholesterol and how it is taken up by the parasite across the multiple membranes that surround it is not fully understood.

Erythrocyte sphingosine kinase regulates intraerythrocytic development of Plasmodium falciparum

January 21, 2021 - 15:31 -- Open Access
Sah RK, Pati S, Saini M, Singh S
Sci Rep. 2021 Jan 13;11(1):1257

The sphingolipid pool is key regulator of vital cellular functions in Plasmodium falciparum a causative agent for deadly malaria. Erythrocytes, the host for asexual stage of Plasmodium, are major reservoir for Sphingosine-1-phosphate (S1P). Erythrocyte possesses Sphingosine kinase (SphK) that catalyzed its biosynthesis from sphingosine (Sph). Since, Plasmodium lacks SphK homologous protein it can be envisaged that it co-opts sphingolipids from both intraerythrocytic as well as extracellular pools for its growth and development. Herein, by sphingosine-NBD probing, we report that infected erythrocytes imports Sph from extracellular pool, which is converted to S1P and thereby taken by P. falciparum.

Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral form for nutrient uptake

January 5, 2021 - 15:06 -- Open Access
Schureck MA, Darling JE, Merk A, Shao J, Daggupati G, Srinivasan P, Olinares PDB, Rout MP, Chait BT, Wollenberg K, Subramaniam S, Desai SA
Elife. 2021 Jan 4;10:e65282

Malaria parasites use the RhopH complex for erythrocyte invasion and channel-mediated nutrient uptake. As the member proteins are unique to Plasmodium spp., how they interact and traffic through subcellular sites to serve these essential functions is unknown. We show that RhopH is synthesized as a soluble complex of CLAG3, RhopH2, and RhopH3 with 1:1:1 stoichiometry.

The molecular basis for peptide-based antimalarial vaccine development targeting erythrocyte invasion by P. falciparum

December 15, 2020 - 14:15 -- Open Access
Aza-Conde J, Reyes C, Suárez CF, Patarroyo MA, Patarroyo ME
Biochem Biophys Res Commun. 2020 Dec 10;534:86-93

This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected.

Plasmodium translocon component EXP2 facilitates hepatocyte invasion

November 10, 2020 - 13:50 -- Open Access
Mello-Vieira J, Enguita FJ, de Koning-Ward TF, Zuzarte-Luís V, Mota MM
Nat Commun. 2020 Nov 6;11(1):5654

Plasmodium parasites possess a translocon that exports parasite proteins into the infected erythrocyte. Although the translocon components are also expressed during the mosquito and liver stage of infection, their function remains unexplored. Here, using a combination of genetic and chemical assays, we show that the translocon component Exported Protein 2 (EXP2) is critical for invasion of hepatocytes.

Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes

October 13, 2020 - 13:01 -- Open Access
Ford A, Kepple D, Lo E, et al.
PLoS Negl Trop Dis. 2020 Oct 12;14(10):e0008234

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity.

Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention

August 13, 2020 - 11:40 -- Open Access
Adderley JD, John von Freyend S, Jackson SA, Bird MJ, Burns AL, Anar B, Metcalf T, Semblat JP, Billker O, Wilson DW, Doerig C
Nat Commun. 2020 Aug 11;11(1):4015

Intracellular pathogens mobilize host signaling pathways of their host cell to promote their own survival. Evidence is emerging that signal transduction elements are activated in a-nucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap through a comprehensive and dynamic assessment of host erythrocyte signaling during infection with Plasmodium falciparum.

NOT Open Access | Designing peptide-based vaccine candidates for Plasmodium falciparum erythrocyte binding antigen 175

July 28, 2020 - 14:44 -- NOT Open Access
Chauhan S, Kumar R, Khan N, Verma S, Sehgal R, Tripathi PK, Farooq U
Biologicals. 2020 Jul 24:S1045-1056(20)30078-6

Plasmodium falciparum leads to a virulent form of malaria. Progress has been achieved in understanding the mechanisms involved in the malarial infection, still there is no effective vaccine to prevent severe infection. An effective vaccine against malaria should be one which can induce immune responses against multiple epitopes in the context of predominantly occurring HLA alleles.

Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity

July 13, 2020 - 16:27 -- Open Access
Han JH, Cho JS, Han ET, et al.
PLoS Negl Trop Dis 14(7): e0008202

Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development.


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