counihan-plasmodiumfalciparum-2017.pdf (3.63 MB)
Download filePlasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate
journal contribution
posted on 2017-03-02, 00:00 authored by Natalie CounihanNatalie Counihan, Scott Chisholm, H E Bullen, A Srivastava, P R Sanders, T K Jonsdottir, G E Weiss, Sreejoyee Ghosh, B S Crabb, D J Creek, P R Gilson, Tania De Koning-WardTania De Koning-WardPlasmodium falciparum 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 Plasmodium-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.
History
Journal
eLifeVolume
6Article number
e23217Pagination
1 - 31Publisher
eLife SciencesLocation
Cambridge, Eng.Publisher DOI
eISSN
2050-084XLanguage
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2017, The AuthorsUsage metrics
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Categories
Keywords
inducible expressionP. bergheicell biologyhost cell remodelinginfectious diseasemicrobiologyrhoptryScience & TechnologyLife Sciences & BiomedicineBiologyLife Sciences & Biomedicine - Other TopicsRED-BLOOD-CELLSHUMAN MALARIA PARASITECLAG MULTIGENE FAMILYRHOPTRY PROTEINPTEX COMPONENTINFECTED ERYTHROCYTESFUNCTIONAL-ANALYSISMEROZOITE INVASIONMAURERS CLEFTSMEMBRANE