Hot, sweet and sticky: the glycobiology of Plasmodium falciparum

Itzstein, Mark von; Plebanski, Magdalena; Cooke, Brian M.; Coppel, Ross L.

doi:10.1016/j.pt.2008.02.007

Cited by 60 publications

(56 citation statements)

References 71 publications

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“…2 and Table 2). The sugar nucleotides detected in the parasite agree well with the monosaccharide contents of known glycoconjugates in P. falciparum consisting of glucosamine (derived from GlcNAc) and Man residues present in GPI anchors and N-glycans (11,14). Furthermore, the detection of UDP-GlcNAc, UDP-Glc, GDP-Man, and GDP-Fuc is consistent with the presence of known or candidate sugar nucleotide biosynthetic enzymes encoded in the genome of P. falciparum (25).…”

Section: Resultssupporting

confidence: 77%

“…In the particular case of the malaria parasite, glycan structures associated with the parasite itself appear to be limited to GPI anchors (11,51) and the recently described N-glycans (14). This seems to confirm the general trend of Plasmodium parasites to reduce several metabolic and biosynthetic pathways and reflects the process of evolving toward a parasitic niche (52).…”

Section: Discussionmentioning

confidence: 58%

“…Sugar Nucleotide Biosynthetic Pathways Predicted in P. falciparum-Based on the current knowledge of P. falciparum sugar biochemistry (11,14,23,32) and the predicted metabolic pathways (25), we have reconstructed the sugar nucleotide biosynthetic routes present in P. falciparum (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…Glycosylphosphatidylinositol (GPI) 4 anchors (10) represent the major carbohydrate modification described in P. falciparum cell surface proteins (11). Several of these GPI-anchored glycoproteins are essential for parasite invasion and virulence (12), and GPI anchors are generated via a complex synthetic pathway (13).…”

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confidence: 99%

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Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum

Sanz

Bandini

Ospina

et al. 2013

Journal of Biological Chemistry

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Background: GDP-fucose and other sugar nucleotide biosynthetic pathways are conserved in the P. falciparum genome. Results: These pathways are active in the intraerythrocytic life cycle of the parasite. Conclusion:The parasite biosynthesizes GDP-fucose and other sugar nucleotides not related to the glycosylphosphatidylinositol structures Significance: Their presence strongly suggests that they are involved in the biosynthesis of glycans not yet characterized.

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Section: Resultssupporting

confidence: 77%

Section: Discussionmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum

Sanz

Bandini

Ospina

et al. 2013

Journal of Biological Chemistry

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“…In several parasites, lineage-specific expansion of some of these interacting domains had led to large protein repertoires, as exemplified by the SAG1 (surface antigen 1) family in Toxoplasma gondii or the DBL (Duffy binding-like) domain in P. falciparum (3). As in many other parasites, the surface of Apicomplexa infective stages is coated mainly by GPI 4 -anchored proteins (4,5). In contrast to transmembrane proteins, such as TRAP or AMA1, essentially conserved in all Apicomplexa (6), the diversity of GPI-anchored protein repertoires appears to depend on the Apicomplexa genus.…”

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confidence: 99%

Structural and Functional Characterization of Bc28.1, Major Erythrocyte-binding Protein from Babesia canis Merozoite Surface

Yang

Murciano

Moubri

et al. 2012

Journal of Biological Chemistry

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Babesiosis (formerly known as piroplasmosis) is a tick-borne disease caused by the intraerythrocytic development of protozoa parasites from the genus Babesia. Like Plasmodium falciparum, the agent of malaria, or Toxoplasma gondii, responsible for human toxoplasmosis, Babesia belongs to the Apicomplexa family. Babesia canis is the agent of the canine babesiosis in Europe. Clinical manifestations of this disease range from mild to severe and possibly lead to death by multiple organ failure. The identification and characterization of parasite surface proteins represent major goals, both for the understanding of the Apicomplexa invasion process and for the vaccine potential of such antigens. Indeed, we have already shown that Bd37, the major antigenic adhesion protein from Babesia divergens, the agent of bovine babesiosis, was able to induce complete protection against various parasite strains. The major merozoite surface antigens of Babesia canis have been described as a 28-kDa membrane protein family, anchored at the surface of the merozoite. Here, we demonstrate that Bc28.1, a major member of this multigenic family, is expressed at high levels at the surface of the merozoite. This protein is also found in the parasite in vitro culture supernatants, which are the basis of effective vaccines against canine babesiosis. We defined the erythrocyte binding function of Bc28.1 and determined its high resolution solution structure using NMR spectroscopy. Surprisingly, although these proteins are thought to play a similar role in the adhesion process, the structure of Bc28.1 from B. canis appears unrelated to the previously published structure of Bd37 from B. divergens. Site-directed mutagenesis experiments also suggest that the mechanism of the interaction with the erythrocyte membrane could be different for the two proteins. The resolution of the structure of Bc28 represents a milestone for the characterization of the parasite erythrocyte binding and its interaction with the host immune system.The phylum Apicomplexa, a large group of single-celled eukaryotic intracellular parasites, includes some of the most important pathogenic parasites of humans and animals, the deadliest of which is the malaria parasite Plasmodium falciparum, responsible for one million human deaths per year and with almost half of the human population at risk of contracting malaria. No vaccine currently exists against P. falciparum, and parasites are becoming increasingly resistant to pharmaceuticals. This is also true for other pathogenic Apicomplexa, such as Toxoplasma, which, together with Plasmodium, challenge global human health improvement programs, and coccidiosis and babesiosis are detrimental for agri-business in both industrialized and developing countries. Babesiosis (formerly known as piroplasmosis) is a tick-borne disease caused by the intraerythrocytic development of an Apicomplexa from the Babesia genus. Hemolytic anemia due to parasite development leads to major symptoms, such as hemoglobinury, fever, asthenia, and renal failure. Amo...

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Plasmodium

Bannister¹,

Sherman²

2009

Encyclopedia of Life Sciences

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Plasmodium is a genus of parasitic protozoa which infect erythrocytes of vertebrates and cause malaria. Their life cycle alternates between mosquito and vertebrate hosts. Parasites enter the bloodstream after a mosquito bite, and multiply sequentially within liver cells and erythrocytes before becoming male or female sexual forms. When ingested by a mosquito, these fuse, then the parasite multiplies again to form more invasive stages which are transmitted back in the insect's saliva to a vertebrate. All invasive stages have specialized secretory structures (apical organelles) typical of the protozoan subphylum Apicomplexa, enabling them to invade cells and tissues. Parasites exploit erythrocytes by ingesting haemoglobin and exporting molecules which change erythrocyte membrane properties. Five species infect humans, the most lethal being Plasmodium falciparum which can cause pathology and death by clogging blood vessels in brain, viscera and placenta. Many hundreds more species infect other mammals, birds and lizards. Key Concepts: Intracellular parasitism. Many apicomplexan protozoa invade and exploit the cells of their hosts, situated in a nutrient‐rich environment and protected from attack by their host's immune system. Alternation of hosts. All parasites of the genus Plasmodium have two different types of host which they parasitize alternately, a vertebrate and a mosquito. This arrangement enables the parasite to multiply numbers greatly in the richly nutrient environment of the vertebrate host, and also to find new hosts via the mosquito vector. The parasitophorous vacuole. Blood stage parasites are enclosed in a cavity within the erythrocyte (parasitophorous vacuole) lined by membrane (parasitophorous vacuole membrane) derived from the erythrocyte surface membrane. The parasite is therefore not in direct contact with the erythrocyte cytoplasm. Life‐cycle stages. The structure, molecular composition and behaviour of Plasmodium parasites change constantly throughout its life cycle, as the expression patterns of its genes vary within both vertebrates and mosquito hosts, enabling parasites to exploit different aspects of the host's biology. Intracellular invasion. Intracellular life requires the ability to selectively capture and enter host cells, seen in the invasion by merozoites into erythrocytes and of sporozoites into liver hepatocytes. In both cases this depends on the secretion of adhesive proteins and membrane‐altering substances by the parasite, and on its actin–myosin driven locomotion. Host cell transformation. Intracellular parasites export various molecules into the host cell to transform its properties. In erythrocytes this increases permeability to nutrients and in some species causes the erythrocyte membrane to adhere to blood vessel walls. The parasite also consumes host cell cytoplasm. Malaria. This is a generic name given to diseases in vertebrates caused by species of Plasmodium . They are typified in mammals by cyclic episodes of fever and may have many other complications including anaemia, spleen pathology, placental dysfunction, neurological complications and in severe malaria, coma and death. Parasite evolution. Molecular studies indicate that the evolution of Plasmodium species is closely linked to the evolution of terrestrial vertebrates and has impacted significantly on the human genome.

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Hot, sweet and sticky: the glycobiology of Plasmodium falciparum

Cited by 60 publications

References 71 publications

Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum

Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum

Structural and Functional Characterization of Bc28.1, Major Erythrocyte-binding Protein from Babesia canis Merozoite Surface

Plasmodium

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