scholarly journals Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum

1991 ◽  
Vol 274 (1) ◽  
pp. 121-132 ◽  
Author(s):  
L L Hsiao ◽  
R J Howard ◽  
M Aikawa ◽  
T F Taraschi
Keyword(s):  
Fatty Acid ◽  
Malaria Parasite ◽  
Phospholipid Composition ◽  
Erythrocyte Membranes ◽  
Fatty Acid Profiles ◽  
Human Malaria Parasite ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Erythrocyte Plasma Membrane ◽  
Fatty Acid Compositions

The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.

scholarly journals Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human malaria parasite Plasmodium falciparum

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 2132-2139 ◽  
Author(s):  
Sean C. Murphy ◽  
Sebastian Fernandez-Pol ◽  
Paul H. Chung ◽  
S. N. Prasanna Murthy ◽  
Stephen B. Milne ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Specific Protein ◽  
Mechanical Perturbation ◽  
Human Malaria Parasite ◽  
Parasite Plasmodium ◽  
Lipid Mass ◽  
Parasite Plasmodium Falciparum ◽  
Blood Stage Infection ◽  
Erythrocyte Plasma Membrane

Abstract Studies of detergent-resistant membrane (DRM) rafts in mature erythrocytes have facilitated identification of proteins that regulate formation of endovacuolar structures such as the parasitophorous vacuolar membrane (PVM) induced by the malaria parasite Plasmodium falciparum. However, analyses of raft lipids have remained elusive because detergents interfere with lipid detection. Here, we use primaquine to perturb the erythrocyte membrane and induce detergent-free buoyant vesicles, which are enriched in cholesterol and major raft proteins flotillin and stomatin and contain low levels of cytoskeleton, all characteristics of raft microdomains. Lipid mass spectrometry revealed that phosphatidylethanolamine and phosphatidylglycerol are depleted in endovesicles while phosphoinositides are highly enriched, suggesting raft-based endovesiculation can be achieved by simple (non–receptor-mediated) mechanical perturbation of the erythrocyte plasma membrane and results in sorting of inner leaflet phospholipids. Live-cell imaging of lipid-specific protein probes showed that phosphatidylinositol (4,5) bisphosphate (PIP2) is highly concentrated in primaquine-induced vesicles, confirming that it is an erythrocyte raft lipid. However, the malarial PVM lacks PIP2, although another raft lipid, phosphatidylserine, is readily detected. Thus, different remodeling/sorting of cytoplasmic raft phospholipids may occur in distinct endovacuoles. Importantly, erythrocyte raft lipids recruited to the invasion junction by mechanical stimulation may be remodeled by the malaria parasite to establish blood-stage infection.

Commitment to sexual differentiation in the human malaria parasite, Plasmodium falciparum

Parasitology ◽  
2000 ◽  
Vol 121 (2) ◽  
pp. 127-133 ◽  
Author(s):  
T. G. SMITH ◽  
P. LOURENÇO ◽  
R. CARTER ◽  
D. WALLIKER ◽  
L. C. RANFORD-CARTWRIGHT
Keyword(s):  
Plasmodium Falciparum ◽  
Sexual Differentiation ◽  
Malaria Parasite ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum

2005 ◽  
Vol 392 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Keizo Yuasa ◽  
Fumika Mi-Ichi ◽  
Tamaki Kobayashi ◽  
Masaya Yamanouchi ◽  
Jun Kotera ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cyclic Nucleotide ◽  
Malaria Parasite ◽  
Catalytic Domain ◽  
Hydrolytic Activity ◽  
Human Malaria Parasite ◽  
Pde Inhibitors ◽  
Ic50 Value ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

This is the first report of molecular characterization of a novel cyclic nucleotide PDE (phosphodiesterase), isolated from the human malaria parasite Plasmodium falciparum and designated PfPDE1. PfPDE1 cDNA encodes an 884-amino-acid protein, including six putative transmembrane domains in the N-terminus followed by a catalytic domain. The PfPDE1 gene is a single-copy gene consisting of two exons and a 170 bp intron. PfPDE1 transcripts were abundant in the ring form of the asexual blood stages of the parasite. The C-terminal catalytic domain of PfPDE1, produced in Escherichia coli, specifically hydrolysed cGMP with a Km value of 0.65 μM. Among the PDE inhibitors tested, a PDE5 inhibitor, zaprinast, was the most effective, having an IC50 value of 3.8 μM. The non-specific PDE inhibitors IBMX (3-isobutyl-1-methylxanthine), theophylline and the antimalarial chloroquine had IC50 values of over 100 μM. Membrane fractions prepared from P. falciparum at mixed asexual blood stages showed potent cGMP hydrolytic activity compared with cytosolic fractions. This hydrolytic activity was sensitive to zaprinast with an IC50 value of 4.1 μM, but insensitive to IBMX and theophylline. Furthermore, an in vitro antimalarial activity assay demonstrated that zaprinast inhibited the growth of the asexual blood parasites, with an ED50 value of 35 μM. The impact of cyclic nucleotide signalling on the cellular development of this parasite has previously been discussed. Thus this enzyme is suggested to be a novel potential target for the treatment of the disease malaria.

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