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.

Keywords: Plasmodium falciparum; field isolate; mass spectrometry; pregnancy-associated malaria; protein abundance; protein identification.