Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes

Alexander G Maier, Melanie Rug, Matthew T O'Neill, Monica Brown, Srabasti Chakravorty, Tadge Szestak, Joanne Chesson, Yang Wu, Katie Hughes, Ross Leon Coppel, Chris Newbold, James G Beeson, Alister Craig, Brendan S Crabb, Alan F Cowman

Research output: Contribution to journalArticleResearchpeer-review

317 Citations (Scopus)

Abstract

A major part of virulence for Plasmodium falciparum malaria infection, the most lethal parasitic disease of humans, results from increased rigidity and adhesiveness of infected host red cells. These changes are caused by parasite proteins exported to the erythrocyte using novel trafficking machinery assembled in the host cell. To understand these unique modifications, we used a large-scale gene knockout strategy combined with functional screens to identify proteins exported into parasite-infected erythrocytes and involved in remodeling these cells. Eight genes were identified encoding proteins required for export of the parasite adhesin PfEMP1 and assembly of knobs that function as physical platforms to anchor the adhesin. Additionally, we show that multiple proteins play a role in generating increased rigidity of infected erythrocytes. Collectively these proteins function as a pathogen secretion system, similar to bacteria and may provide targets for antivirulence based therapies to a disease responsible for millions of deaths annually.
Original languageEnglish
Pages (from-to)48 - 61
Number of pages14
JournalCell
Volume134
Issue number1
Publication statusPublished - 2008

Cite this

Maier, A. G., Rug, M., O'Neill, M. T., Brown, M., Chakravorty, S., Szestak, T., ... Cowman, A. F. (2008). Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell, 134(1), 48 - 61.
Maier, Alexander G ; Rug, Melanie ; O'Neill, Matthew T ; Brown, Monica ; Chakravorty, Srabasti ; Szestak, Tadge ; Chesson, Joanne ; Wu, Yang ; Hughes, Katie ; Coppel, Ross Leon ; Newbold, Chris ; Beeson, James G ; Craig, Alister ; Crabb, Brendan S ; Cowman, Alan F. / Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. In: Cell. 2008 ; Vol. 134, No. 1. pp. 48 - 61.
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abstract = "A major part of virulence for Plasmodium falciparum malaria infection, the most lethal parasitic disease of humans, results from increased rigidity and adhesiveness of infected host red cells. These changes are caused by parasite proteins exported to the erythrocyte using novel trafficking machinery assembled in the host cell. To understand these unique modifications, we used a large-scale gene knockout strategy combined with functional screens to identify proteins exported into parasite-infected erythrocytes and involved in remodeling these cells. Eight genes were identified encoding proteins required for export of the parasite adhesin PfEMP1 and assembly of knobs that function as physical platforms to anchor the adhesin. Additionally, we show that multiple proteins play a role in generating increased rigidity of infected erythrocytes. Collectively these proteins function as a pathogen secretion system, similar to bacteria and may provide targets for antivirulence based therapies to a disease responsible for millions of deaths annually.",
author = "Maier, {Alexander G} and Melanie Rug and O'Neill, {Matthew T} and Monica Brown and Srabasti Chakravorty and Tadge Szestak and Joanne Chesson and Yang Wu and Katie Hughes and Coppel, {Ross Leon} and Chris Newbold and Beeson, {James G} and Alister Craig and Crabb, {Brendan S} and Cowman, {Alan F}",
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Maier, AG, Rug, M, O'Neill, MT, Brown, M, Chakravorty, S, Szestak, T, Chesson, J, Wu, Y, Hughes, K, Coppel, RL, Newbold, C, Beeson, JG, Craig, A, Crabb, BS & Cowman, AF 2008, 'Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes', Cell, vol. 134, no. 1, pp. 48 - 61.

Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. / Maier, Alexander G; Rug, Melanie; O'Neill, Matthew T; Brown, Monica; Chakravorty, Srabasti; Szestak, Tadge; Chesson, Joanne; Wu, Yang; Hughes, Katie; Coppel, Ross Leon; Newbold, Chris; Beeson, James G; Craig, Alister; Crabb, Brendan S; Cowman, Alan F.

In: Cell, Vol. 134, No. 1, 2008, p. 48 - 61.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes

AU - Maier, Alexander G

AU - Rug, Melanie

AU - O'Neill, Matthew T

AU - Brown, Monica

AU - Chakravorty, Srabasti

AU - Szestak, Tadge

AU - Chesson, Joanne

AU - Wu, Yang

AU - Hughes, Katie

AU - Coppel, Ross Leon

AU - Newbold, Chris

AU - Beeson, James G

AU - Craig, Alister

AU - Crabb, Brendan S

AU - Cowman, Alan F

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Maier AG, Rug M, O'Neill MT, Brown M, Chakravorty S, Szestak T et al. Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell. 2008;134(1):48 - 61.