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

Natalie A. Counihan, Scott A. Chisholm, Hayley E. Bullen, Anubhav Srivastava, Paul R. Sanders, Thorey K. Jonsdottir, Greta E Weiss, Sreejoyee Ghosh, Brendan S Crabb, Darren J Creek, Paul R Gilson, Tania F. De Koning-Ward

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere23217
Number of pages31
JournaleLife
Volume6
DOIs
Publication statusPublished - 2 Mar 2017

Cite this

Counihan, N. A., Chisholm, S. A., Bullen, H. E., Srivastava, A., Sanders, P. R., Jonsdottir, T. K., ... De Koning-Ward, T. F. (2017). Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate. eLife, 6, [e23217]. https://doi.org/10.7554/eLife.23217
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. / Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate. In: eLife. 2017 ; Vol. 6.
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abstract = "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.",
author = "Counihan, {Natalie A.} and Chisholm, {Scott A.} and Bullen, {Hayley E.} and Anubhav Srivastava and Sanders, {Paul R.} and Jonsdottir, {Thorey K.} and Weiss, {Greta E} and Sreejoyee Ghosh and Crabb, {Brendan S} and Creek, {Darren J} and Gilson, {Paul R} and {De Koning-Ward}, {Tania F.}",
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Counihan, NA, Chisholm, SA, Bullen, HE, Srivastava, A, Sanders, PR, Jonsdottir, TK, Weiss, GE, Ghosh, S, Crabb, BS, Creek, DJ, Gilson, PR & De Koning-Ward, TF 2017, 'Plasmodium falciparum parasites deploy RhopH2 into the host erythrocyte to obtain nutrients, grow and replicate', eLife, vol. 6, e23217. https://doi.org/10.7554/eLife.23217

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

In: eLife, Vol. 6, e23217, 02.03.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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.

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N2 - 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.

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.

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