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

Abstract

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.

The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1

“…A slight reduction in the rigidity of infected cells was observed, but was not statistically significant [58]. However, a proteomic analysis of field isolates from patients with cerebral or uncomplicated malaria found that PF3D7_0402000 was upregulated in cerebral malaria isolates relative to the uncomplicated malaria strains, possibly suggesting a more important role for PF3D7_0402000 in pathogenesis in humans [68]. …”

Comprehensive proteomics investigation of P. vivax-infected human plasma and parasite isolates

“…Around the same time, Bachmann et al, reported potential muscle damage and microvasculature lesions during the course of cerebral malaria based on elevated muscle protein levels in the plasma of children with cerebral malaria [14]. Recently, an MS-based proteomics study comparing 9 complicated malaria (CM) and 10 uncomplicated malaria (UM) patient samples reported the association of selected P. falciparum proteins with the pathophysiology of cerebral malaria [15].…”

Systems Biology-Based Investigation of Host–Plasmodium Interactions

“…In particular, significantly higher expression of Plasmodium MESA/PfEMP2 protein was seen in patients with cerebral malaria. This protein is an antigen that is exported from mature Plasmodium parasites and interacts with the host erythrocyte cytoskeleton and surface membrane [31][32][33]. This result highlights the importance of proteomics data in supporting the results of transcriptomics data, especially when previously published studies may have reported conflicting results.…”