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PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.

Jonsdottir TK, Elsworth B, Cobbold S, Gabriela M, Ploeger E, Parkyn Schneider M, Charnaud SC, Dans MG, McConville M, Bullen HE, Crabb BS, Gilson PR

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  • Journal PLoS pathogens

  • Published 31 Jul 2023

  • Volume 19

  • ISSUE 7

  • Pagination e1011006

  • DOI 10.1371/journal.ppat.1011006

Abstract

A key element of Plasmodium biology and pathogenesis is the trafficking of ~10% of the parasite proteome into the host red blood cell (RBC) it infects. To cross the parasite-encasing parasitophorous vacuole membrane, exported proteins utilise a channel-forming protein complex termed the Plasmodium translocon of exported proteins (PTEX). PTEX is obligatory for parasite survival, both in vitro and in vivo, suggesting that at least some exported proteins have essential metabolic functions. However, to date only one essential PTEX-dependent process, the new permeability pathways, has been described. To identify other essential PTEX-dependant proteins/processes, we conditionally knocked down the expression of one of its core components, PTEX150, and examined which pathways were affected. Surprisingly, the food vacuole mediated process of haemoglobin (Hb) digestion was substantially perturbed by PTEX150 knockdown. Using a range of transgenic parasite lines and approaches, we show that two major Hb proteases; falcipain 2a and plasmepsin II, interact with PTEX core components, implicating the translocon in the trafficking of Hb proteases. We propose a model where these proteases are translocated into the PV via PTEX in order to reach the cytostome, located at the parasite periphery, prior to food vacuole entry. This work offers a second mechanistic explanation for why PTEX function is essential for growth of the parasite within its host RBC.