Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes
- Author(s)
- 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;
- Details
- Publication Year 2008-07-11,Volume 134,Issue #1,Page 48-61
- Journal Title
- CELL
- Publication Type
- Journal Article
- 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.
- Publisher
- CELL PRESS
- Keywords
- RED-BLOOD-CELL; DOUBLE CROSSOVER RECOMBINATION; TARGETED GENE DELETION; NEGATIVE SELECTION; MALARIA VIRULENCE; HOST ERYTHROCYTE; MEMBRANE; CYTOADHERENCE; SURFACE; PARASITE
- Publisher's Version
- https://doi.org/10.1016/j.cell.2008.04.051
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-07-11 12:00:00