title: Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes.
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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Maier
authors.forename: Melanie
authors.initials: M
authors.lastname: Rug
authors.forename: Matthew T
authors.initials: MT
authors.lastname: O'Neill
authors.forename: Monica
authors.initials: M
authors.lastname: Brown
authors.forename: Srabasti
authors.initials: S
authors.lastname: Chakravorty
authors.forename: Tadge
authors.initials: T
authors.lastname: Szestak
authors.forename: Joanne
authors.initials: J
authors.lastname: Chesson
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Katie
authors.initials: K
authors.lastname: Hughes
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.forename: Chris
authors.initials: C
authors.lastname: Newbold
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.forename: Alister
authors.initials: A
authors.lastname: Craig
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D048430:Cell Shape; D004910:Erythrocyte Membrane / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000378:metabolism / Q000472:pathogenicity*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum