The parasitophorous vacuole nutrient channel is critical for drug access in malaria parasites and modulates the artemisinin resistance fitness cost.
EXP1
PVM
Plasmodium falciparum
amino acids
antimalaria drugs, Kelch13
artemisinin resistance
malaria
nutrient permeable channel
nutrients
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 12 2021
08 12 2021
Historique:
received:
14
05
2021
revised:
14
09
2021
accepted:
03
11
2021
pubmed:
6
12
2021
medline:
19
1
2022
entrez:
5
12
2021
Statut:
ppublish
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
Identifiants
pubmed: 34863371
pii: S1931-3128(21)00508-4
doi: 10.1016/j.chom.2021.11.002
pii:
doi:
Substances chimiques
Amino Acids
0
Antimalarials
0
Artemisinins
0
artemisinin
9RMU91N5K2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1774-1787.e9Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.