Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut

Anil K. Ghosh, Isabelle Coppens, Henrik Gårdsvoll, Michael Ploug, Marcelo Jacobs-Lorena

Research output: Contribution to journalArticlepeer-review

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 showthat enolase lines the ookinete surface. An antienolase antibody inhibits oocyst development of both Plasmodiumberghei and Plasmodiumfalciparum, 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.

Original languageEnglish (US)
Pages (from-to)17153-17158
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number41
DOIs
StatePublished - Oct 11 2011

Keywords

  • Insect vectors of disease
  • Transmission-blocking vaccines

ASJC Scopus subject areas

  • General

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