title: Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut.
abstract: Ookinete invasion of the mosquito midgut is an essential step for the development of the malaria parasite in the mosquito. Invasion involves recognition between a presumed mosquito midgut receptor and an ookinete ligand. Here, we show that enolase lines the ookinete surface. An antienolase antibody inhibits oocyst development of both Plasmodium berghei and Plasmodium falciparum, suggesting that enolase may act as an invasion ligand. Importantly, we demonstrate that surface enolase captures plasminogen from the mammalian blood meal via its lysine motif (DKSLVK) and that this interaction is essential for midgut invasion, because plasminogen depletion leads to a strong inhibition of oocyst formation. Although addition of recombinant WT plasminogen to depleted serum rescues oocyst formation, recombinant inactive plasminogen does not, thus emphasizing the importance of plasmin proteolytic activity for ookinete invasion. The results support the hypothesis that enolase on the surface of Plasmodium ookinetes plays a dual role in midgut invasion: by acting as a ligand that interacts with the midgut epithelium and, further, by capturing plasminogen, whose conversion to active plasmin promotes the invasion process.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coppens
authors.forename: Henrik
authors.initials: H
authors.lastname: Gårdsvoll
authors.forename: Michael
authors.initials: M
authors.lastname: Ploug
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D004064:Digestive System / Q000469:parasitology; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology; D008954:Models, Biological; D033661:Oocysts / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000502:physiology; D010958:Plasminogen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010962:Plasmodium berghei / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D010958:Plasminogen; D010751:Phosphopyruvate Hydratase