Characterization of Plasmodium falciparum sexual stage antigens and their biosynthesis in synchronised gametocyte cultures

Vermeulen, A.N.; Deursen, Jan van; Brakenhoff, Ruud H.; Lensen, T; Ponnudurai, T.; Meuwissen, J. H. E. T.

doi:10.1016/0166-6851(86)90027-7

Cited by 107 publications

(48 citation statements)

References 16 publications

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“…Fourth, the reported effective size of Gal␤1-4GlcNAcol on Bio-Gel P-4 was 2 GU or less (23), a figure not in agreement with the reported effective sizes of galactitol, N-acetylgalactosaminitol, and Hex␤1-4GlcNAcol of 1.5, 2.6, and 3.2, respectively (52), raising doubts about the authenticity of the characterized structure. Finally, whereas we and others (18,28) found that uninfected erythrocytes do not metabolically incorporate sugars into their proteins to significant levels, Dieckmann-Shuppert et al (23) reported that the level of 14 GlcN incorporation into proteins of control red cells was about half the level of incorporation into proteins of red cells with 10% parasitemia (27). The latter is not plausible, considering that UDP-GlcNAc is not synthesized by uninfected red cells (27).…”

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confidence: 64%

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Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

Gowda

Gupta

Davidson

1997

Journal of Biological Chemistry

131

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The nature and extent of carbohydrate modification in intraerythrocytic stage Plasmodium falciparum proteins have been controversial. This study describes the characterization of the carbohydrates in intraerythrocytic P. falciparum proteins and provides an overall picture of the nature of carbohydrate modification in the parasite proteins. P. falciparum strains were metabolically labeled with radioactive sugar precursors and ethanolamine at different developmental stages. The individual parasite proteins separated on SDS-polyacrylamide gels and whole parasite cell lysates were analyzed for the carbohydrate moieties. The results established the following: 1) glycosylphosphatidylinositol (GPI) anchors represent the major carbohydrate modification in the intraerythrocytic stage P. falciparum proteins; 2) in contrast to previous reports, O-linked carbohydrates are either absent or present only at very low levels in the parasite; and 3) P. falciparum contains low levels of N-glycosylation capability. The amount of N-linked carbohydrates in whole parasite proteins is ϳ6% compared with the GPI anchors attached to proteins based on radioactive GlcN incorporated into the proteins.The glycan cores of multiple parasite protein GPI anchors are all similar, consisting of protein-ethanolamine-phosphate-(Man␣1-2)6Man␣1-2Man␣1-6Man␣1-4GlcN. The fourth Man residues distal to GlcN of the GPI anchor glycan cores contain unidentified substituents that are susceptible to conditions of nitrous acid deamination. This unusual structural feature may contribute to the reported pathogenic properties of the P. falciparum GPI anchors.Malaria, a life-threatening disease caused by parasitic protozoa of the genus Plasmodium, is a major health problem throughout the tropical and subtropical regions of the world. Among the four species that infect humans, Plasmodium falciparum is the most virulent. New approaches such as vaccine development and novel therapeutic agents are urgently needed due to the emergence of parasite strains resistant to chloroquine and other commonly used drugs (1).Vaccines based on antigens of the blood stage parasite are under intensive study. A major focus has been on synthetic peptides or recombinant proteins of cell surface antigens (2-6). However, this approach has not been highly effective, although immunization with native cell surface proteins purified from the erythrocytic stage parasite is known to confer significant protective immunity (7-10). It is plausible that post-translational modifications play an important role in antigenicity. Accordingly, a basic understanding of such modifications may assist in the development of effective vaccines.Glycosylation is an often extensive post-translational modification of eukaryotic proteins. Carbohydrate moieties of glycoproteins perform a variety of functions including modulation of immunological properties, receptor-ligand interactions, sorting and localization of proteins, cell adhesion, and cell-cell communication (11). In addition, they contribute to protein conform...

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confidence: 64%

“…Several proteins of erythrocytic stage P. falciparum are known to contain carbohydrates (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The deduced amino acid sequences of the parasite proteins have potential N-glycosylation sites (7, 24 -26).…”

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confidence: 99%

Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

Gowda

Gupta

Davidson

1997

Journal of Biological Chemistry

131

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“…Generally, the protein is only found after zygotes formation within the mosquito (i.e., 0.5-2 hours after the blood meal). 13,23,24 However, there has been one report of low level synthesis of Pfs25 in immature P. falciparum gametocytes in culture, 25 and at least in P. berghei, high levels of P25 mRNA are present in gametocytes. 24,26 Thus, there is a potential for low levels of expression in the vertebrate host that could provide a source of antigen for boosting of B cell memory.…”

Section: Discussionmentioning

confidence: 99%

Induction of Transmission-Blocking Immunity in Aotus Monkeys by Vaccination With a Plasmodium Vivax Clinical Grade Pvs25 Recombinant Protein

Arévalo‐Herrera

Solarte

Yasnot

et al. 2005

The American Journal of Tropical Medicine and Hygiene

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Abstract. Aotus monkeys were used to determine the immunogenicity of Pvs25 protein expressed in the zygote/ ookinete surface. Animals were immunized in three times with 100 g of Pvs25 formulated in Montanide ISA-720. Antibodies to Pvs25 detected by an enzyme-linked immunosorbent assay appeared by day 30 after the first immunization, with a peak of antibodies levels on day 150. These antibodies were still detectable on day 300. Plasma samples on day 150 from experimental group were able to completely block the development of the parasite in Anopheles albimanus mosquitoes artificially fed with human isolates of Plasmodium vivax. Immunized Aotus monkeys were infected with blood forms of the P. vivax Salvador I strain and no boosting effect of blood infection on titers of antibodies to Pvs25 was observed despite the presence of infective gametocytes. In conclusion, Pvs25 protein formulated in Montanide ISA-720 induces efficient and long-lasting transmission-blocking antibodies that cannot be boosted by parasite infection.

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“…The remaining six coded for two heat shock proteins (PFI0875, PF08 0054), three nonannotated hypothetical proteins (PF10 0164, PF14 0744, PF13 0338), and one member of the PfSep protein family [23] (PF11 0040). The entire data set was also inspected for expression levels of genes encoding known sexual stagespecific proteins which appear at later stages of gametocyte maturation, such as Pfs45/48 and Pfs230, produced since stage II gametocytes [24], Pftubulin-␣II and Pfg377, since stage III [25,26], Pfs230II, specific for stage V male gametocytes [27], and Pfs25, appearing in gametes [28]. This analysis showed that none of these mRNAs was upregulated in 3D7 parasites (Table III, supplementary information), which confirmed morphological observations that sexual differentiation was still at an early phase in the 3D7 cultures analysed and, importantly, that mRNAs from mature gametocytes were not significantly contributing to the RNA pool obtained from 3D7 parasites.…”

Section: Pairwise Comparison Of 3d7 and F12 Transcriptomesmentioning

confidence: 99%

Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum

Silvestrini

Bozdech

Lanfrancotti

et al. 2005

Molecular and Biochemical Parasitology

141

147

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A genome-wide expression analysis was undertaken to identify novel genes specifically activated from early stages of gametocytogenesis in Plasmodium falciparum. A comparative analysis was conducted on sexually induced cultures of reference parasite clone 3D7 and its gametocyteless derivative clone F12. Competitive hybridisations on long-oligomer microarrays representing 4488 P. falciparum genes identified a remarkably small number of transcripts differentially produced in the two clones. Upregulation of the mRNAs for the early gametocyte markers Pfs16 and Pfg27 was however readily detected in 3D7, and such genes were used as reference transcripts in a comparative time course analysis of 3D7 and F12 parasites between 30 and 40 h post-invasion in cultures induced to enter gametocytogenesis. One hundred and seventeen genes had expression profiles which correlated to those of pfs16 and pfg27, and Northern blot analysis and published proteomic data identified those whose expression was gametocyte-specific. Immunofluorescence analysis with antibodies against two of these gene products identified two novel parasite membrane associated, sexual stage-specific proteins. One was produced from stage I gametocytes and the second showed peak production in stage II gametocytes. The two proteins were named Pfpeg-3 and Pfpeg-4, for P. falciparum proteins of early gametocytes.

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Characterization of Plasmodium falciparum sexual stage antigens and their biosynthesis in synchronised gametocyte cultures

Cited by 107 publications

References 16 publications

Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

Glycosylphosphatidylinositol Anchors Represent the Major Carbohydrate Modification in Proteins of Intraerythrocytic Stage Plasmodium falciparum

Induction of Transmission-Blocking Immunity in Aotus Monkeys by Vaccination With a Plasmodium Vivax Clinical Grade Pvs25 Recombinant Protein

Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum

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