Exported Proteins Required for Virulence and Rigidity of Plasmodium falciparum-Infected Human Erythrocytes

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作者：

Alexander G. Maier， Melanie Rug， Matthew T. O\"Neill， Monica Brown， Srabasti Chakravorty， Tadge Szestak， Joanne Chesson， Yang Wu， Katie Hughes， Ross L. Coppel， Chris Newbold， James G. Beeson， Alister Craig， Brendan S. Crabb， Alan F. Cowman

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摘要：

A major part of virulence forPlasmodium falciparummalaria 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.

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关键词：

HUMDISEASE CELLBIO

DOI：

10.1016/j.cell.2008.04.051

被引量：

486

年份：

2008