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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asexual blood forms of the human malaria parasite, Plasmodium falciparum, synthesize a major glycosylated 195 kDa protein that has been considered for the development of a vaccine. beta-Elimination-borohydride reduction of the 195 kDa glycoprotein and its 16 kDa processed product after metabolic labeling of their carbohydrates, showed the presence of derived, labeled glucosaminitol and alanine. This suggests that the 195 and 16 kDa glycoproteins contain distinct O-glycosyl linkages and that N-acetylglucosamine and serine residues are involved in the attachment of carbohydrate moieties to the protein core. Endo-O-glycanase treatment of total glycoproteins shows that O-glycosidycally-linked sugars represent a major carbohydrate moiety in P. falciparum glycoproteins.
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PMID:Plasmodium falciparum synthesizes O-glycosylated glycoproteins containing O-linked N-acetylglucosamine. 162 79

Malaria parasites (ookinetes) appear to digest the peritrophic membrane in the mosquito midgut during penetration. Previous studies demonstrated that lectins specific for N-acetylglucosamine bind to the peritrophic membrane and proposed that the membrane contains chitin [Rudin, W. & Hecker, H. (1989) Parasitol. Res. 75, 268-279]. In the present study, we show that the peritrophic membrane is digested by Serratia marcescens chitinase (EC 3.2.1.14), leading to the release of N-acetylglucosamine and fragmentation of the membrane. We also report the presence of a malaria parasite chitinase that digests 4-methylumbelliferyl chitotriose. The enzyme is not detectable until 15 hr after zygote formation, the time required for maturation of the parasite from a zygote to an ookinete, the invasive form of the parasite. At 20 hr, the enzyme begins to appear in the culture supernatant. The chitinase extracted from the parasite and found in the culture supernatant consists of a major band and two minor bands of activity on native polyacrylamide gel electrophoresis. The presence of chitin in the peritrophic membrane, the disruption of the peritrophic membrane during invasion, and the presence of chitinase in ookinetes suggest that the chitinase in ookinetes is used in the penetration of the peritrophic membrane.
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PMID:Malaria parasite chitinase and penetration of the mosquito peritrophic membrane. 201 89

The soluble amphiphilic glycoprotein, Ag1 (gp60), purified from supernatants of in vitro cultures of Plasmodium falciparum has a molecular mass of 60 kDa and did not exhibit size variation in the different P. falciparum isolates tested by immunoblotting. Ag1 was shown to interact with the lectin Erythrina christagalli agglutinin, which is specific for carbohydrates bearing beta-D-galactose(1-4)-D-N-acetylglucosamine. Indirect immunofluorescence studies showed that Ag1 is located on the surface of trophozoites and schizonts but not on the surface of merozoites. Ag1 is recognized by human immune sera from six different malaria-endemic regions. Ag1 induces in vitro proliferation of lymphocytes from malaria-immune individuals in an antigen-specific manner.
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PMID:Biochemical characterization, localization and immunostimulating properties of a soluble glycoprotein, Ag1, isolated from in vitro cultures of Plasmodium falciparum. 225 Dec 41

Attempts to control human malaria by immunological means could be compromised by antigenic variability within and between different strains of malarial parasites1. A useful alternative approach might be to block parasite antigens which are important in the mechanisms of invasion of red cells. As the major human parasite Plasmodium falciparum is highly specific for human red cells, isolation of the proteins involved in the recognition of red cells by this parasite might be of particular value. Recent studies suggest that the major red cell sialoglycoproteins (SGPs), glycophorins A, B and possibly C, may carry the sites recognized by the parasite2-4. Furthermore, because certain carbohydrates present on SGPs such as N-acetylglucosamine are able to block invasion by the parasite5, they may be involved in the initial interaction between parasite and red cell. We have now identified parasite proteins which bind to SGP or N-acetylglucosamine on Sepharose 4B columns. Three proteins, of molecular weights (MWs) 140,000 (140K), 70K and 35K, seem to be specifically bound by N-acetylglucosamine.
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PMID:Lectin-like polypeptides of P. falciparum bind to red cell sialoglycoproteins. 633 94

Glycophorin both in solution and inserted into liposomes blocks invasion of erythrocytes by the malaria parasite Plasmodium falciparum. Furthermore, one sugar, N-acetyl-D-glucosamine (GlcNAc), completely blocks invasion of the erythrocyte by this parasite. GlcNAc coupled to bovine serum albumin to prevent the sugar entering infected erythrocytes was at least 100,000 times more effective than GlcNAc alone. Bovine serum albumin coupled to lactose or bovine serum albumin alone had no effect on invasion. These results suggest that the binding of P. falciparum to erythrocytes is lectin-like and is determined by carbohydrates on glycophorin.
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PMID:A lectin-like receptor is involved in invasion of erythrocytes by Plasmodium falciparum. 634 86

O-Glycosylation is the major form of protein glycosylation in human erythrocytes infected with the asexual intraerythrocytic stage of the malaria parasite. Plasmodium falciparum. This study compares aspects of O-glycosylation in P. falciparum-infected and uninfected erythrocytes. Non-labeled and metabolically glucosamine-labeled O-glycans were obtained from the protein fraction of infected or uninfected erythrocytes by beta elimination. Additional label was introduced by reduction with sodium borohydride, or by the attachment of radioactive Gal to peripheral GlcNAc using galactosyltransferase. 2-4-times more labeled O-glycans were obtained from infected erythrocytes compared to the same number of uninfected ones, consistent with additional biosynthesis by the parasite. Our analysis of these O-glycans showed no significant qualitative divergence between the O-glycans of the infected and those of the uninfected red cell. According to preliminary alditol analyses, the O-glycans of P. falciparum-infected red cells do not contain GalNAc at their reducing terminus. Moreover, GalNAc was not synthesized by P. falciparum from either Glc, Gal, GlcN or GalN. At least one O-glycan found in P. falciparum-infected erythrocytes contains GlcNAc at its reducing terminus. Gel-filtration results had suggested the presence of O-GlcNAc on proteins in the infected erythrocyte. Probing with a synthetic pentapeptide, we could show that P. falciparum expresses its own O-GlcNAc transferase during intraerythrocytic development. Using this peptide, the enzyme was characterized to some degree. The localization and function of O-GlcNAc in P. falciparum remains to be elucidated.
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PMID:Studies on O-glycans of Plasmodium-falciparum-infected human erythrocytes. Evidence for O-GlcNAc and O-GlcNAc-transferase in malaria parasites. 840 96

The major pathways of glucose metabolism in the malaria parasite, Plasmodium falciparum, have now been elucidated, and the structures and properties of parasite-specific enzymes are presently being investigated. Little is known, however, about the enzymes catalysing monosaccharide interconversions in the parasite. In the present investigation we have examined the pathway of N-acetylglucosamine catabolism which, in higher organisms, involves the following reaction sequence: N-acetylglucosamine -->N-acetylglucosamine 6-phosphate-->glucosamine 6-phosphate-->fructose 6-phosphate. Assay of the specific kinase (E.C. 2.7.1.59) catalysing the phosphorylation of the sugar showed that the enzyme is present in Plasmodium extracts as well as in normal human erythrocytes; specific activities of 7.2 and 5.3 nmol/h/mg protein were measured for the parasite and erythrocyte extracts, respectively, N-Acetylglucosamine 6-phosphate deacetylase (E.C. 3.5.1.25), catalysing the second reaction, was also detected in both normal and Plasmodium-infected erythrocytes. At 75% parasitaemia, the deacetylase activity was close to 3 times higher than that of normal control cells. The erythrocyte deacetylase was purified approximately 16,000-fold by chromatography on DE52 cellulose, chromatofocusing, and size exclusion chromatography. Attempts to purify the parasite enzyme by the same procedures were unsuccessful due to loss of activity. A partially purified erythrocyte deacetylase preparation (eluted from DE52 cellulose) had a pH optimum of 7.5, a pI of 6.0, as indicated by chromatofocusing, and a K(m) of 29 microM. In conjunction with previous investigations, the present study indicated that all three enzymes required for N-acetylglucosamine utilization are present in Plasmodium parasites as well as in normal erythrocytes.
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PMID:N-acetylglucosamine kinase and N-acetylglucosamine 6-phosphate deacetylase in normal human erythrocytes and Plasmodium falciparum. 898 40

Present-day catarrhines (old world monkeys and hominoids) lack Gal alpha1-3 Gal beta1-4 GlcNAc-R structures (alpha-galactosyl epitopes) and produce the corresponding anti-galactosyl antibodies (anti-gal), while platyrrhines (new world monkeys) and non-primate mammals possess alpha-galactosyl epitopes and lack anti-gal. Anti-gal is shown to inhibit Plasmodium falciparum growth in culture in a concentration dependent manner. probably by binding to alpha-galactosyl epitopes on merozoite surface molecules and causing complement mediated damage. A P. falciparum-like malaria parasite may therefore have selected for the inactivation of an alpha 1-3 galactosyl transferase in catarrhines. The implications of the results for the development of clinical immunity to falciparum malaria are briefly discussed.
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PMID:Association of malaria with inactivation of alpha1,3-galactosyl transferase in catarrhines. 919 66

Mannans and its related compounds decelerated human (Hu) red blood cell (RBC)-clearance in severe combined immunodeficiency (SCID) mice by inhibiting erythro-phagocytosis of macrophages. Chimeric SCID mice for Hu-RBC which are generated by repeated transfusions with mature Hu-RBCs are described recently as a model for Plasmodium falciparum infection, though the Hu-RBC clearance in the mice at present is very rapid and the parasitemia in the mice is only erratic. Here, we aimed to study the method to decelerate Hu-RBC clearance in SCID mice, to establish a suitable mouse model for malaria parasites. Yeast and Candida mannans as well as lactoferrin, a glycoprotein containing both oligomannoside- and N-acetyllactosamine-type glycans, decelerated Hu-RBC clearance, but instead other saccharides such as carboxymethyl chitin, N-acetylglucosamine, and D-glucose did not. Yeast mannan and lactoferrin interfered significantly with in vitro Hu-RBC-phagocytosis which was also inhibited by mannopentaose and mannotoriose. D-mannose exhibited a moderate inhibitory activity. N-acetyl-D-glucosamine, however, showed only a slight inhibitory activity, but D-glucose had no inhibitory activity on Hu-RBC phagocytosis. These results may postulate that Hu-RBC clearance in SCID mouse might be mediated by receptor-ligand binding by a macrophage lectin like receptor with mannose specificity.
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PMID:Mannan decelerates the clearance of human red blood cells in SCID mouse. 950 21

Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 3.2.1.14) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P. gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC(50) (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P. gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase.
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PMID:The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences. 1057 Jan 98


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