title: Plasmodium falciparumparasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate.
abstract: Plasmodium falciparumparasites, 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) inPlasmodium-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.
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Australia.
authors.forename: Natalie A
authors.identifier: 0000-0002-8973-3344
authors.initials: NA
authors.lastname: Counihan
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Australia.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Chisholm
authors.affiliation: Burnet Institute, Melbourne, Australia.
authors.forename: Hayley E
authors.initials: HE
authors.lastname: Bullen
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors.forename: Anubhav
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Burnet Institute, Melbourne, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanders
authors.affiliation: Burnet Institute, Melbourne, Australia.|Department of Medicine, University of Melbourne, Parkville, Australia.
authors.forename: Thorey K
authors.initials: TK
authors.lastname: Jonsdottir
authors.affiliation: Burnet Institute, Melbourne, Australia.
authors.forename: Greta E
authors.initials: GE
authors.lastname: Weiss
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Australia.
authors.forename: Sreejoyee
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Burnet Institute, Melbourne, Australia.|Department of Medicine, University of Melbourne, Parkville, Australia.|Monash University, Melbourne, Australia.
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Creek
authors.affiliation: Burnet Institute, Melbourne, Australia.|Monash University, Melbourne, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gilson
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Australia.
authors.forename: Tania F
authors.identifier: 0000-0001-5810-8063
authors.initials: TF
authors.lastname: de Koning-Ward
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism; D014815:Vitamins / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D011743:Pyrimidines; D014815:Vitamins; C073168:rhoptry-associated antigen-2, Plasmodium
keywords: Inducible expression; P. berghei; cell biology; host cell remodeling; infectious disease; microbiology; rhoptry