TY - JOUR TI - Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate AU - Counihan, Natalie A AU - Chisholm, Scott A AU - Bullen, Hayley E AU - Srivastava, Anubhav AU - Sanders, Paul R AU - Jonsdottir, Thorey K AU - Weiss, Greta E AU - Ghosh, Sreejoyee AU - Crabb, Brendan S AU - Creek, Darren J AU - Gilson, Paul R AU - de Koning-Ward, Tania F A2 - Soldati-Favre, Dominique VL - 6 PY - 2017 DA - 2017/03/02 SP - e23217 C1 - eLife 2017;6:e23217 DO - 10.7554/eLife.23217 UR - https://doi.org/10.7554/eLife.23217 AB - Plasmodium 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. KW - P. berghei KW - rhoptry KW - host cell remodeling KW - Inducible expression JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -