Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes

Luciano A. Moreira, Junitsu Ito, Anil Ghosh, Martin Devenport, Helge Zieler, Eappen G. Abraham, Andrea Crisanti, Tony Nolan, Flaminia Catteruccia, Marcelo Jacobs-Lorena

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Malaria kills millions of people every year, and new control measures are urgently needed. The recent demonstration that (effector) genes can be introduced into the mosquito germ line to diminish their ability to transmit the malaria parasite offers new hope toward the fight of the disease (Ito, J., Ghosh, A., Moreira, L. A., Wimmer, E. A. & Jacobs-Lorena, M. (2002) Nature, 417, 452-455). Because of the high selection pressure that an effector gene imposes on the parasite population, development of resistant strains is likely to occur. In search of additional antiparasitic effector genes, we have generated transgenic Anopheles stephensi mosquitoes that express the bee venom phospholipase A2 (PLA2) gene from the gut-specific and blood-inducible Anopheles gambiae carboxypeptidase (AgCP) promoter. Northern blot analysis indicated that the PLA2 mRNA is specifically expressed in the guts of transgenic mosquitoes with peak expression at ∼4 h after blood ingestion. Western blot and immunofluorescence analyses detected PLA2 protein in the midgut epithelia of transgenic mosquitoes from 8 to 24 h after a blood meal. Importantly, transgene expression reduced Plasmodium berghei oocyst formation by 87% on average and greatly impaired transmission of the parasite to naive mice. The results indicate that PLA2 may be used as an additional effector gene to block the development of the malaria parasite in mosquitoes.

Original languageEnglish (US)
Pages (from-to)40839-40843
Number of pages5
JournalJournal of Biological Chemistry
Volume277
Issue number43
DOIs
StatePublished - Oct 25 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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