Differential protein expression profiles between Plasmodium falciparum parasites isolated from subjects presenting with pregnancy-associated malaria and uncomplicated malaria in Benin.

Abstract

BACKGROUND:

Plasmodium falciparum is responsible for severe malaria, including pregnancy-associated malaria (PAM). During intra-erythrocytic maturation, the infected erythrocyte (iE) membrane is modified by insertion of parasite-derived proteins, primarily consisting of variant surface antigens such as P. falciparum erythrocyte membrane protein-1.

METHODS:

To identify new PAM-specific parasite membrane proteins, we conducted a mass spectrometry-based proteomic study and compared the protein expression profiles of 10 PAM and 10 uncomplicated malaria (UM) samples.

RESULTS:

We focused on the 454/1139 membrane-associated and hypothetical proteins for comparative analysis. Using filter-based feature-selection methods combined with supervised data analysis, we identified a subset of 53 proteins that distinguished PAM and UM samples. Up to 19/20 samples were correctly assigned to their respective clinical group. A hierarchical clustering analysis of these 53 proteins based on the similarity of their expression profiles revealed 2 main clusters of 40 and 13 proteins that were under- or over-expressed, respectively, in PAM.

CONCLUSIONS:

VAR2CSA is identified and associated with PAM, validating our experimental approach. Other PAM-predictive proteins included PFI1785w, PF14_0018, PFB0115w, PFF0325c, and PFA_0410w. These proteomics data demonstrate the involvement of selected proteins in the pathophysiology of PAM, providing new insights for the definition of potential new targets for a vaccine against PAM.

• Authors: Gwladys I Bertin, Audrey Sabbagh, François Guillonneau, Sayeh Jafari-Guemouri, Sem Ezinmegnon, Christian Federici, Benjamin Hounkpatin, Nadine Fievet, Philippe Deloron
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 208 Issue 12 Pg. 1987-97 (Dec 15 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23901091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Protozoan Proteins

Topics

• Adult
• Benin (epidemiology)
• Child
• Cluster Analysis
• Female
• Humans
• Malaria, Falciparum (parasitology)
• Male
• Mass Spectrometry
• Membrane Proteins (chemistry, classification, metabolism)
• Parasitemia (parasitology)
• Plasmodium falciparum (metabolism, pathogenicity)
• Pregnancy
• Pregnancy Complications, Parasitic (parasitology)
• Principal Component Analysis
• Protozoan Proteins (chemistry, classification, metabolism)
• Reproducibility of Results