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

Apoorva Venkatesh,Swati Patankar,Shalini Aggarwal,Vipin Kumar,Swati Kumar,Sheetal Bankar,Jayanthi Shastri,Srushti Rajyaguru,Sanjeeva Srivastava

doi:10.1186/s12879-020-4885-3

Abstract

BackgroundIn recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective against P. falciparum. A deeper understanding of P. vivax biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited P. vivax research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria.MethodsA mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins.ResultsThirty-eight P. vivax proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant P. vivax proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three Plasmodium exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates.ConclusionsA parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against P. vivax also depend on early diagnosis. This work provides deeper insights into the biology of P. vivax by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.

Highlights

In recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes
Identification of P. vivax proteins in human plasma The human plasma proteome was analyzed to identify P. vivax proteins that may be secreted during the asexual stages of the parasite’s life cycle and those that persist in circulation after erythrocyte rupture
Based on the total number of parasite proteins detected per individual, samples were segregated into two groups; Group A (1–4 parasite proteins in plasma) and Group B (> 20 parasite proteins in plasma)

Summary

Introduction

Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. A deeper understanding of P. vivax biology and pathogenesis is, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. Unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria. P. vivax malaria is a public health concern in the tropical and sub-tropical regions of the world. The last few years have witnessed a surge in the number of severe vivax malaria cases [2, 3], posing a serious threat to health and economy. It is important to design and implement interventions targeting P. vivax for its control and elimination [7]

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