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Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression.

Tuikue Ndam N, Bischoff E, Proux C, Lavstsen T, Salanti A, Guitard J, Nielsen MA, Coppée JY, Gaye A, Theander T, David PH, Deloron P - PLoS ONE (2008)

Bottom Line: The proportion of PAM over-expressed genes located in subtelomeric regions as well as that of PAM over-expressed genes predicted to be exported were higher than expected compared to the whole genome.These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM.These data may be very valuable for future vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche pour le Développement, UR010 at Université Paris Descartes, Mother and Child Health in the Tropics, Faculté de Pharmacie, Paris, France. Nicaise.Ndam@ird.fr

ABSTRACT

Background: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances on the molecular basis of virulence and immune evasion have helped identify var2csa as a PAM-specific var gene.

Methodology/principal findings: The present study presents a genome-wide microarray transcript analysis of 18 P. falciparum parasite isolates freshly collected from the placenta. The proportion of PAM over-expressed genes located in subtelomeric regions as well as that of PAM over-expressed genes predicted to be exported were higher than expected compared to the whole genome. The identification of novel parasite molecules with specificity to PAM and which are likely involved in host-pathogen interactions and placental tropism is described. One of these proteins, PFI1785w, was further characterized as the product of a two-exon PHIST gene, and was more often recognized by serum samples from P. falciparum-exposed women than from men.

Conclusions/significance: These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM. These data may be very valuable for future vaccine development.

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Related in: MedlinePlus

Recognition of PFI1785w recombinant protein (NP561) by sera from malaria exposed individuals assessed by ELISA.ELISA was carried out on NP561, DBL5-ε of VAR2CSA and GLURP coated plates. The levels of IgG expressed as OD values are shown for exposed Ghanaian men (n = 30; white bars) and women (n = 30; grey bars). The top, bottom, and line through the middle of the box correspond to the 75th percentile, 25th percentile, and 50th percentile (median), respectively. The whiskers on the bottom extend from the 10th percentile and top 90th percentile. Plasma concentrations of anti-VAR2CSA and anti-NP561 IgG were significantly higher in the women group.
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pone-0001855-g005: Recognition of PFI1785w recombinant protein (NP561) by sera from malaria exposed individuals assessed by ELISA.ELISA was carried out on NP561, DBL5-ε of VAR2CSA and GLURP coated plates. The levels of IgG expressed as OD values are shown for exposed Ghanaian men (n = 30; white bars) and women (n = 30; grey bars). The top, bottom, and line through the middle of the box correspond to the 75th percentile, 25th percentile, and 50th percentile (median), respectively. The whiskers on the bottom extend from the 10th percentile and top 90th percentile. Plasma concentrations of anti-VAR2CSA and anti-NP561 IgG were significantly higher in the women group.

Mentions: Part of the corresponding protein encoded by PFI1785w was expressed in baculovirus transfected insect cells and purified as a secreted HIS protein (that we called NP561). NP561 was recognized in ELISA by serum samples from individuals living in endemic areas (Ghana). Sera from women had significantly higher levels of antibodies against NP561 compared to sera from men of the same area in Ghana (p = 0.04). Recognition of another parasite recombinant protein (GLURP) was also measured and no significant difference was observed between sera from both genders (Figure 5).


Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression.

Tuikue Ndam N, Bischoff E, Proux C, Lavstsen T, Salanti A, Guitard J, Nielsen MA, Coppée JY, Gaye A, Theander T, David PH, Deloron P - PLoS ONE (2008)

Recognition of PFI1785w recombinant protein (NP561) by sera from malaria exposed individuals assessed by ELISA.ELISA was carried out on NP561, DBL5-ε of VAR2CSA and GLURP coated plates. The levels of IgG expressed as OD values are shown for exposed Ghanaian men (n = 30; white bars) and women (n = 30; grey bars). The top, bottom, and line through the middle of the box correspond to the 75th percentile, 25th percentile, and 50th percentile (median), respectively. The whiskers on the bottom extend from the 10th percentile and top 90th percentile. Plasma concentrations of anti-VAR2CSA and anti-NP561 IgG were significantly higher in the women group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2267001&req=5

pone-0001855-g005: Recognition of PFI1785w recombinant protein (NP561) by sera from malaria exposed individuals assessed by ELISA.ELISA was carried out on NP561, DBL5-ε of VAR2CSA and GLURP coated plates. The levels of IgG expressed as OD values are shown for exposed Ghanaian men (n = 30; white bars) and women (n = 30; grey bars). The top, bottom, and line through the middle of the box correspond to the 75th percentile, 25th percentile, and 50th percentile (median), respectively. The whiskers on the bottom extend from the 10th percentile and top 90th percentile. Plasma concentrations of anti-VAR2CSA and anti-NP561 IgG were significantly higher in the women group.
Mentions: Part of the corresponding protein encoded by PFI1785w was expressed in baculovirus transfected insect cells and purified as a secreted HIS protein (that we called NP561). NP561 was recognized in ELISA by serum samples from individuals living in endemic areas (Ghana). Sera from women had significantly higher levels of antibodies against NP561 compared to sera from men of the same area in Ghana (p = 0.04). Recognition of another parasite recombinant protein (GLURP) was also measured and no significant difference was observed between sera from both genders (Figure 5).

Bottom Line: The proportion of PAM over-expressed genes located in subtelomeric regions as well as that of PAM over-expressed genes predicted to be exported were higher than expected compared to the whole genome.These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM.These data may be very valuable for future vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche pour le Développement, UR010 at Université Paris Descartes, Mother and Child Health in the Tropics, Faculté de Pharmacie, Paris, France. Nicaise.Ndam@ird.fr

ABSTRACT

Background: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances on the molecular basis of virulence and immune evasion have helped identify var2csa as a PAM-specific var gene.

Methodology/principal findings: The present study presents a genome-wide microarray transcript analysis of 18 P. falciparum parasite isolates freshly collected from the placenta. The proportion of PAM over-expressed genes located in subtelomeric regions as well as that of PAM over-expressed genes predicted to be exported were higher than expected compared to the whole genome. The identification of novel parasite molecules with specificity to PAM and which are likely involved in host-pathogen interactions and placental tropism is described. One of these proteins, PFI1785w, was further characterized as the product of a two-exon PHIST gene, and was more often recognized by serum samples from P. falciparum-exposed women than from men.

Conclusions/significance: These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM. These data may be very valuable for future vaccine development.

Show MeSH
Related in: MedlinePlus