Fiche publication


Date publication

novembre 2021

Journal

Cell host & microbe

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DAVIOUD-CHARVET Elisabeth , Dr ELHABIRI Mourad


Tous les auteurs :
Mesén-Ramírez P, Bergmann B, Elhabiri M, Zhu L, von Thien H, Castro-Peña C, Gilberger TW, Davioud-Charvet E, Bozdech Z, Bachmann A, Spielmann T

Résumé

Intraerythrocytic malaria parasites proliferate bounded by a parasitophorous vacuolar membrane (PVM). The PVM contains nutrient permeable channels (NPCs) conductive to small molecules, but their relevance for parasite growth for individual metabolites is largely untested. Here we show that growth-relevant levels of major carbon and energy sources pass through the NPCs. Moreover, we find that NPCs are a gate for several antimalarial drugs, highlighting their permeability properties as a critical factor for drug design. Looking into NPC-dependent amino acid transport, we find that amino acid shortage is a reason for the fitness cost in artemisinin-resistant (ART) parasites and provide evidence that NPC upregulation to increase amino acids acquisition is a mechanism of ART parasites in vitro and in human infections to compensate this fitness cost. Hence, the NPCs are important for nutrient and drug access and reveal amino acid deprivation as a critical constraint in ART parasites.

Mots clés

EXP1, PVM, Plasmodium falciparum, amino acids, antimalaria drugs, Kelch13, artemisinin resistance, malaria, nutrient permeable channel, nutrients

Référence

Cell Host Microbe. 2021 Nov 30;: