Clinical proteomics of the neglected human malarial parasite Plasmodium vivax

Abstract

Recent reports highlight the severity and the morbidity of disease caused by the long neglected malaria parasite Plasmodium vivax. Due to inherent difficulties in the laboratory-propagation of P. vivax, the biology of this parasite has not been adequately explored. While the proteome of P. falciparum, the causative agent of cerebral malaria, has been extensively explored from several sources, there is limited information on the proteome of P. vivax. We have, for the first time, examined the proteome of P. vivax isolated directly from patients without adaptation to laboratory conditions. We have identified 153 proteins from clinical P. vivax, majority of which do not show homology to any previously known gene products. We also report 29 new proteins that were found to be expressed in P. vivax for the first time. In addition, several proteins previously implicated as anti-malarial targets, were also found in our analysis. Most importantly, we found several unique proteins expressed by P. vivax.This study is an important step in providing insight into physiology of the parasite under clinical settings.

Figure 1. Mass spectrometric analysis of proteins employed by asexual stages of P. vivax.

A. Giemsa-stained image of peripheral blood smear of P. vivax infected patient. B. SDS-PAGE profile of proteins extracted from asexual stages of P. vivax by sequential lysis using SDS buffer (lane 1), urea containing buffer (lane 2) and direct boiling of pellet in Laemmli buffer (lane 3). C. Represents the Total Ion Chromatogram (TIC), MS, and MS/MS spectra for enolase (PVX_095015).

Figure 2. Functional profiles of protein expressed by asexual stages of P. vivax.

A. Proteins identified in asexual stages were plotted as a function of their broad functional classification as defined in PlasmoDB or GO. Only one class was assigned to one protein to avoid any redundancy. Major group in the P. vivax is represented by hypothetical proteins followed by metabolic enzymes, chaperones and proteins involved in virulence. B. Showing functional plot for hypothetical proteins. About 25% of the hypothetical proteins were assigned to different functional classes on domain architecture.

Figure 3. Interaction network of the proteins identified in P. vivax from patient.

Interaction network of P. vivax proteins detected in our study has been constructed based on the presence of interactions of their P. falciparum homologs. The P. vivax proteins which have been detected in our study have been colored as red nodes. Many proteins detected in P. vivax from malaria patients form highly interconnected hubs showing the regulatory role of these proteins in several processes in vivax malaria. The major nodes have been indicated with an enlarged font and are hyperlinked to PlasmoDB.

Figure 4. Schematic representations of pathways operational in the P. vivax from patient.

The figure depicts the cellular localization of the identified proteins. Proteins indicated in blue represent the ones detected in the clinical isolate of P. vivax and black shows the pathways they are involved in. ‘’ indicates potential targets for anti-malarials.