A Systematic Targeted Genetic Screen Identifies Proteins Involved in Cytoadherence of the Malaria Parasite P. falciparum

TL;DR

This study identifies new parasite proteins involved in malaria's ability to stick to blood vessels, using genetic screening to uncover factors important for disease progression.

Contribution

A systematic genetic screen identifies novel proteins involved in cytoadherence of P. falciparum.

Findings

Three genetically modified parasite lines showed adhesion defects.

One line had a block in PfEMP1 transport or folding.

The study highlights essential genes for blood-stage parasite survival.

Abstract

Immediately after invading their chosen host cell, the mature human erythrocyte, malaria parasites begin to export an array of proteins to this compartment, where they initiate processes that are prerequisite for parasite survival and propagation, including nutrient import and immune evasion. One consequence of these activities is the emergence of novel adhesive phenotypes that can lead directly to pathology in the human host. To identify parasite proteins involved in this process, we used modern genetic tools to target genes encoding 15 exported parasite proteins, selected by an in silico workflow. This resulted in four genetically modified parasite lines that were then characterised in detail. Of these lines, three could be shown to have aberrations in adhesion, and of these one appears to have a block in the transport and/or correct folding of the major surface adhesin PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1). Our data expand the known factors involved in this important process and once again highlight the complexity of this phenomenon.

In silico workflow for selection of genes targeted in this study. We have identified a number of proteins involved in host cell modification by malaria parasites. Furthermore, we highlight a number of genes that appear to be essential for blood‐stage survival of these parasites.

Figures