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

Maier, A. G., Rug, M., O'Neill, M. T., Brown, M., Chakravorty, S., Szestak, Tadge, Chesson, J., Wu, Yang, Hughes, K., Coppel, R. L., Newbold, C., Beeson, J. G., Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164, Crabb, B. S. and Cowman, A. F. (2008) 'Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes'. Cell, Vol 134, Issue 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 anti-virulence based therapies to a disease responsible for millions of deaths annually.

Item Type:	Article
Uncontrolled Keywords:	red-blood-cell double crossover recombination targeted gene deletion negative selection malaria virulence host erythrocyte membrane cytoadherence surface parasite
Subjects:	QX Parasitology > Protozoa > QX 135 Plasmodia WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.cell.2008.04.051
Depositing User:	Mary Creegan
Date Deposited:	31 Aug 2010 09:49
Last Modified:	17 Jul 2019 14:13
URI:	https://archive.lstmed.ac.uk/id/eprint/849

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