Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes.
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 approximately 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.
Moreira
Luciano A
LA
Department of Genetics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4955, USA.
Ito
Junitsu
J
Ghosh
Anil
A
Devenport
Martin
M
Zieler
Helge
H
Abraham
Eappen G
EG
Crisanti
Andrea
A
Nolan
Tony
T
Catteruccia
Flaminia
F
Jacobs-Lorena
Marcelo
M
D000818:Animals; D030801:Animals, Genetically Modified / Q000469:parasitology*; D000852:Anopheles / Q000469:parasitology*; D001483:Base Sequence; D001514:Bee Venoms / Q000201:enzymology*; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000235:genetics / Q000502:physiology*; D054467:Phospholipases A2; D010962:Plasmodium berghei / Q000254:growth & development*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D001514:Bee Venoms; D017931:DNA Primers; D011994:Recombinant Proteins; D010741:Phospholipases A; D054467:Phospholipases A2