Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte

TLDR

Malaria parasites export remodeling and virulence proteins into the erythrocyte, traversing parasite, parasitophorous vacuole, and erythrocyte membranes to establish infection. The study demonstrates that a conserved pentameric sequence is central to protein export and predicts the exported proteome in *Plasmodium falciparum*. We identified 400 putative erythrocyte‑targeted proteins (~8 % of genes), including 225 virulence and 160 remodeling proteins, and the conserved export signal across *Plasmodium* species suggests new antimalarial targets.

Abstract

To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in Plasmodium falciparum . We identified 400 putative erythrocyte-targeted proteins corresponding to ∼8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across Plasmodium species has implications for the development of new antimalarials.