Differential Protein Expression Profiles Between Plasmodium falciparum Parasites Isolated From Subjects Presenting With Pregnancy-Associated Malaria and Uncomplicated Malaria in Benin

Bertin, Gwladys; Sabbagh, Audrey; Guilhot, François; Jafari-Guemouri, Sayeh; Ezinmègnon, Sèm; Federici, Christian; Hounkpatin, Benjamin; Fiévet, Nadine; Deloron, Philippe

doi:10.1093/infdis/jit377

Cited by 20 publications

(26 citation statements)

References 40 publications

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“…Genes annotated "phista-like" or as "phist" genes were grouped together as "phist others." Yellow boxes to the right of the heat map indicate PHIST proteins present in the early gametocyte proteome (35), differentially expressed phist genes in pregnancy-associated malaria (29,49,50,84,92,112) and in cerebral malaria (32,34), or if variant expression has been reported (55). Green to red colors represent fold changes (log fold changes from Ϫ3 to 3).…”

Section: Pf3d7_0102200 (Resa)mentioning

confidence: 99%

Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling

Warncke

Vakonakis

Beck

2016

Microbiol Mol Biol Rev

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SUMMARYDuring the asexual cycle,Plasmodium falciparumextensively remodels the human erythrocyte to make it a suitable host cell. A large number of exported proteins facilitate this remodeling process, which causes erythrocytes to become more rigid, cytoadherent, and permeable for nutrients and metabolic products. Among the exported proteins, a family of 89 proteins, called thePlasmodiumhelical interspersed subtelomeric (PHIST) protein family, has been identified. While also found in otherPlasmodiumspecies, the PHIST family is greatly expanded inP. falciparum. Although a decade has passed since their first description, to date, most PHIST proteins remain uncharacterized and are of unknown function and localization within the host cell, and there are few data on their interactions with other host or parasite proteins. However, over the past few years, PHIST proteins have been mentioned in the literature at an increasing rate owing to their presence at various localizations within the infected erythrocyte. Expression of PHIST proteins has been implicated in molecular and cellular processes such as the surface display of PfEMP1, gametocytogenesis, changes in cell rigidity, and also cerebral and pregnancy-associated malaria. Thus, we conclude that PHIST proteins are central to host cell remodeling, but despite their obvious importance in pathology, PHIST proteins seem to be understudied. Here we review current knowledge, shed light on the definition of PHIST proteins, and discuss these proteins with respect to their localization and probable function. We take into consideration interaction studies, microarray analyses, or data from blood samples from naturally infected patients to combine all available information on this protein family.

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Section: Pf3d7_0102200 (Resa)mentioning

confidence: 99%

Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling

Warncke

Vakonakis

Beck

2016

Microbiol Mol Biol Rev

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“…In addition to VAR2CSA, several conserved proteins expressed by placental parasites have been identified [ 66 – 69 ]. These conserved proteins may play an independent role in IE adhesion, or may interact with VAR2CSA to form conformational epitopes targeted by naturally acquired immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Comparative transcriptome analyses identified 11 genes that were upregulated in placental parasites compared to children’s parasites [ 66 ] and 38 genes in placental parasites compared to the reference parasite line 3D7 [ 67 ]. Two comparative proteomics analyses of placental parasites identified 17 and 53 conserved proteins respectively that were expressed exclusively or at higher levels in placental parasites than in parasites collected from children [ 68 , 69 ]. Because these novel genes and proteins are upregulated in VAR2CSA-expressing parasites, studies should be undertake to determine whether deletion of VAR2CSA may influence their expression or localization.…”

Section: Invariant Proteins Expressed By Placental Parasitesmentioning

confidence: 99%

Designing a VAR2CSA-based vaccine to prevent placental malaria

Fried

Duffy

2015

Vaccine

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Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1–2 pregnancies as they acquire antibodies that block adhesion to CSA. The protein VAR2CSA, a member of the PfEMP1 variant surface antigen family, mediates parasite adhesion to CSA, and is the leading target for a vaccine to prevent PM. Obstacles to PM vaccine development include the large size (~350 kD), high cysteine content, and sequence variation of VAR2CSA. A number of approaches have been taken to identify the combination of VAR2CSA domains and alleles that can induce broadly active antibodies that block adhesion of heterologous parasite isolates to CSA. This review summarizes these approaches, which have examined VAR2CSA fragments for binding activity, antigenicity with naturally acquired antibodies, and immunogenicity in animals for inducing anti-adhesion or surface-reactive antibodies. Two products are expected to enter human clinical studies in the near future based on N-terminal VAR2CSA fragments that have high binding affinity for CSA, and additional proteins preferentially expressed by placental parasites are also being examined for their potential contribution to a PM vaccine.

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“…The lysate of each sample was transferred in RIPA (Radio-ImmunoPrecipitation Assay) buffer with 2% SDS and 1X protease inhibitor (Roche), and stored at −80 °C. One hundred μg of proteins were reduced, alkylated, and digested with 1 μg/μl of trypsin overnight at 37 °C according to Bertin and al 2431…”

Section: Methodsmentioning

confidence: 99%

“…CM and UM samples used in this study were collected at Cotonou in Benin as described 31 . Briefly, CM patients were recruited with a Blantyre score ≤ 2 at the university medical center and the Lagune Mother and Child hospital.…”

Section: Methodsmentioning

confidence: 99%

Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria

Bertin

Sabbagh

Argy

et al. 2016

Sci Rep

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Plasmodium falciparum is responsible of severe malaria, including cerebral malaria (CM). During its intra-erythrocytic maturation, parasite-derived proteins are expressed, exported and presented at the infected erythrocyte membrane. To identify new CM-specific parasite membrane proteins, we conducted a mass spectrometry-based proteomic study and compared the protein expression profiles between 9 CM and 10 uncomplicated malaria (UM) samples. Among the 1097 Plasmodium proteins identified, we focused on the 499 membrane-associated and hypothetical proteins for comparative analysis. Filter-based feature selection methods combined with supervised data analysis identified a subset of 29 proteins distinguishing CM and UM samples with high classification accuracy. A hierarchical clustering analysis of these 29 proteins based on the similarity of their expression profiles revealed two clusters of 15 and 14 proteins, respectively under- and over-expressed in CM. Among the over-expressed proteins, the MESA protein is expressed at the erythrocyte membrane, involved in proteins trafficking and in the export of variant surface antigens (VSAs), but without antigenic function. Antigen 332 protein is exported at the erythrocyte, also involved in protein trafficking and in VSAs export, and exposed to the immune system. Our proteomics data demonstrate an association of selected proteins in the pathophysiology of CM.

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Differential Protein Expression Profiles Between Plasmodium falciparum Parasites Isolated From Subjects Presenting With Pregnancy-Associated Malaria and Uncomplicated Malaria in Benin

Cited by 20 publications

References 40 publications

Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling

Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling

Designing a VAR2CSA-based vaccine to prevent placental malaria

Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria

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