Glycobiology ofPlasmodium falciparum: An emerging area of research

Dc, Hoessli; Ea, Davidson; Rt, Schwarz; Nasiruddin, .

doi:10.1007/bf01049673

Cited by 22 publications

(5 citation statements)

References 31 publications

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“…The presence of N-linked glycoproteins in P. falciparum, mainly in the ring and young-trophozoite stages of the intraerythrocytic cycle, has been unequivocally demonstrated [2], in spite of reports claiming that glycosylation in the malaria parasite is mostly associated with the synthesis of glycosylphosphatidylinositol-anchor structures [3,40]. Nevertheless, our results on the presence of N-glycosylation in P. falciparum glycoproteins prompted us to study the effects of inhibitors of this biosynthetic pathway on parasite growth.…”

Section: Discussionmentioning

confidence: 81%

Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: presence of dolichols of 11 and 12 isoprene units

et al. 1999

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N-glycosylation of proteins is required for the intra-erythrocytic schizogony of Plasmodium falciparum. In eukaryotic cells, this process involves the transfer of oligosaccharides from a dolichyl pyrophosphate derivative to asparagine residues. We have identified dolichol, dolichyl phosphate and dolichyl pyrophosphate species of 11 and 12 isoprenoid residues by metabolic labelling with [(3)H]farnesyl pyrophosphate, [(3)H]geranylgeranyl pyrophosphate and [(14)C]acetate in the different intra-erythrocytic stages of P. falciparum. This is the first demonstration of short-chain dolichols in the phylum Apicomplexa. The results demonstrate the presence of an active isoprenoid pathway in the intra-erythrocytic stages of P. falciparum. Parasites treated with mevastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, show depressed biosynthesis of dolichol, dolichyl phosphate and isoprenoid pyrophosphate. This effect is observed in all intra-erythrocytic stages of the parasite life cycle, but is most pronounced in the ring stage. N-linked glycosylation of proteins was inhibited in the ring and young-trophozoite stages after mevastatin treatment of parasite cultures. Therefore the isoprenoid pathway may represent a different approach to the development of new anti-malarial drugs.

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Section: Discussionmentioning

confidence: 81%

Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: presence of dolichols of 11 and 12 isoprene units

et al. 1999

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“…Negatively charged glycosaminoglycans (GAGs) such as heparan sulfate (HS) and chondroitin sulfate A (CSA) are well distributed on the endothelial cell surface. The potential participation of these GAGs in the merozoite invasion, cytoadherence, and rosetting processes has drawn special attention from malaria researchers (8,33,60,113). Heparin and HS were found to inhibit P. falciparum merozoite invasion of erythrocytes and to disrupt malaria rosetting (26,33).…”

Section: Endothelial Receptors For Adhesionmentioning

confidence: 99%

Molecular Aspects of Severe Malaria

2000

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SUMMARY Human infections with Plasmodium falciparum may result in severe forms of malaria. The widespread and rapid development of drug resistance in P. falciparum and the resistance of the disease-transmitting mosquitoes to insecticides make it urgent to understand the molecular background of the pathogenesis of malaria to enable the development of novel approaches to combat the disease. This review focuses on the molecular mechanisms of severe malaria caused by the P. falciparum parasite. The nature of severe malaria and the deleterious effects of parasite-derived toxins and host-induced cytokines are introduced. Sequestration, brought about by cytoadherence and rosetting, is linked to severe malaria and is mediated by multiple receptors on the endothelium and red blood cells. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the ligand responsible for a majority of binding interactions, and the multiply adhesive features of this sticky molecule are presented. Antigenic variation is also a major feature of PfEMP1 and of the surface of the P. falciparum-infected erythrocyte. Possible mechanisms of P. falciparum antigenic variation in asexual stages are further discussed. We conclude this review with a perspective and suggestions of important aspects for future investigations.

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“…The potential participation of these GAGs in the merozoite invasion, cytoadherence, and rosetting processes has drawn special attention from malaria researchers (8,33,60,113). Heparin and HS were found to inhibit P. falciparum merozoite invasion of erythrocytes and to disrupt malaria rosetting (26,33).…”

Section: Endothelial Receptors For Adhesionmentioning

confidence: 99%