Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate

parasites, the causative agents of malaria, modify their host erythrocyte to render them permeable to supplementary nutrient uptake from the plasma and for removal of toxic waste. Here we investigate the contribution of the rhoptry protein RhopH2, in the formation of new permeability pathways (NPPs)...

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Bibliographic Details
Published in:eLife 2017-03, Vol.6
Main Authors: Counihan, Natalie A, Chisholm, Scott A, Bullen, Hayley E, Srivastava, Anubhav, Sanders, Paul R, Jonsdottir, Thorey K, Weiss, Greta E, Ghosh, Sreejoyee, Crabb, Brendan S, Creek, Darren J, Gilson, Paul R, de Koning-Ward, Tania F
Format: Article
Language:English
Subjects:
Animals
Cell Biology
Cofactors
Cytoskeleton
Cytoskeleton - metabolism
Erythrocytes
Erythrocytes - parasitology
Genes
Genetically modified organisms
host cell remodeling
Host-Pathogen Interactions
Humans
Inducible expression
Malaria
Metabolites
Mice
Microbiology and Infectious Disease
Nutrient uptake
Nutrients
P. berghei
Parasites
Permeability
Plasmodium
Plasmodium falciparum
Plasmodium falciparum - growth & development
Plasmodium falciparum - metabolism
Principal components analysis
Proteins
Protozoan Proteins - metabolism
Pyrimidines
Pyrimidines - metabolism
rhoptry
Rhoptry protein
Roles
Software
Solutes
Vitamins
Vitamins - metabolism
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Summary:parasites, the causative agents of malaria, modify their host erythrocyte to render them permeable to supplementary nutrient uptake from the plasma and for removal of toxic waste. Here we investigate the contribution of the rhoptry protein RhopH2, in the formation of new permeability pathways (NPPs) in -infected erythrocytes. We show RhopH2 interacts with RhopH1, RhopH3, the erythrocyte cytoskeleton and exported proteins involved in host cell remodeling. Knockdown of RhopH2 expression in cycle one leads to a depletion of essential vitamins and cofactors and decreased de novo synthesis of pyrimidines in cycle two. There is also a significant impact on parasite growth, replication and transition into cycle three. The uptake of solutes that use NPPs to enter erythrocytes is also reduced upon RhopH2 knockdown. These findings provide direct genetic support for the contribution of the RhopH complex in NPP activity and highlight the importance of NPPs to parasite survival.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.23217