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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

Transcriptional characteristics of placental isolates.Plots of log2 ratio of expression (M) against average log intensity (A) for three different pools of placental isolates (pool 1 included 3 isolates: ≤5% rings, 70% trophozoites, ≥25% schizonts; pool 2 with 7 isolates: ≤5% rings, ≥25% trophozoites, 70% schizonts; pool 3 with 8 isolates: ≤5% rings, 0% trophozoites, ≥95% schizonts) versus common 3D7 reference (10% rings, 45% trophozoites, 45% schizonts). Only statistically significant data according to Bonferroni p value correction are shown. A single dominant var gene (var2csa) is detected in placental isolates of all groups examined (red dots; each dot represents one oligonucleotide). Non var genes over-expressed or under-expressed are shown as black (when the difference was present in all 3 pools), green (in 2 of the 3 pools). Blue dots correspond to oligonucleotides corresponding to genes only differentially expressed in 1 out of 3 experiments (these were not taken into account in our analysis).
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pone-0001855-g001: Transcriptional characteristics of placental isolates.Plots of log2 ratio of expression (M) against average log intensity (A) for three different pools of placental isolates (pool 1 included 3 isolates: ≤5% rings, 70% trophozoites, ≥25% schizonts; pool 2 with 7 isolates: ≤5% rings, ≥25% trophozoites, 70% schizonts; pool 3 with 8 isolates: ≤5% rings, 0% trophozoites, ≥95% schizonts) versus common 3D7 reference (10% rings, 45% trophozoites, 45% schizonts). Only statistically significant data according to Bonferroni p value correction are shown. A single dominant var gene (var2csa) is detected in placental isolates of all groups examined (red dots; each dot represents one oligonucleotide). Non var genes over-expressed or under-expressed are shown as black (when the difference was present in all 3 pools), green (in 2 of the 3 pools). Blue dots correspond to oligonucleotides corresponding to genes only differentially expressed in 1 out of 3 experiments (these were not taken into account in our analysis).

Mentions: Using the Bonferroni adjustment method, 84 genes consistently displayed similar differential expression profiles in 2 out of 3 groups (over-expressed N = 38; under-expressed N = 46) (Figure 1, Table 1). These genes generally had highly abundant transcripts either in the test samples or in the 3D7 reference pool as judged by spot fluorescence values. Var2csa was the only var gene unambiguously over-expressed. Over-expression in placental parasites was observed in 14 out of 18 different var2csa oligonucleotides (data not shown). Other var hybridising probes showing transcript abundance differentials represented either truncated or pseudo-genes or var exon2, [17].


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)

Transcriptional characteristics of placental isolates.Plots of log2 ratio of expression (M) against average log intensity (A) for three different pools of placental isolates (pool 1 included 3 isolates: ≤5% rings, 70% trophozoites, ≥25% schizonts; pool 2 with 7 isolates: ≤5% rings, ≥25% trophozoites, 70% schizonts; pool 3 with 8 isolates: ≤5% rings, 0% trophozoites, ≥95% schizonts) versus common 3D7 reference (10% rings, 45% trophozoites, 45% schizonts). Only statistically significant data according to Bonferroni p value correction are shown. A single dominant var gene (var2csa) is detected in placental isolates of all groups examined (red dots; each dot represents one oligonucleotide). Non var genes over-expressed or under-expressed are shown as black (when the difference was present in all 3 pools), green (in 2 of the 3 pools). Blue dots correspond to oligonucleotides corresponding to genes only differentially expressed in 1 out of 3 experiments (these were not taken into account in our analysis).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001855-g001: Transcriptional characteristics of placental isolates.Plots of log2 ratio of expression (M) against average log intensity (A) for three different pools of placental isolates (pool 1 included 3 isolates: ≤5% rings, 70% trophozoites, ≥25% schizonts; pool 2 with 7 isolates: ≤5% rings, ≥25% trophozoites, 70% schizonts; pool 3 with 8 isolates: ≤5% rings, 0% trophozoites, ≥95% schizonts) versus common 3D7 reference (10% rings, 45% trophozoites, 45% schizonts). Only statistically significant data according to Bonferroni p value correction are shown. A single dominant var gene (var2csa) is detected in placental isolates of all groups examined (red dots; each dot represents one oligonucleotide). Non var genes over-expressed or under-expressed are shown as black (when the difference was present in all 3 pools), green (in 2 of the 3 pools). Blue dots correspond to oligonucleotides corresponding to genes only differentially expressed in 1 out of 3 experiments (these were not taken into account in our analysis).
Mentions: Using the Bonferroni adjustment method, 84 genes consistently displayed similar differential expression profiles in 2 out of 3 groups (over-expressed N = 38; under-expressed N = 46) (Figure 1, Table 1). These genes generally had highly abundant transcripts either in the test samples or in the 3D7 reference pool as judged by spot fluorescence values. Var2csa was the only var gene unambiguously over-expressed. Over-expression in placental parasites was observed in 14 out of 18 different var2csa oligonucleotides (data not shown). Other var hybridising probes showing transcript abundance differentials represented either truncated or pseudo-genes or var exon2, [17].

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