The Glutathione Biosynthetic Pathway of Plasmodium Is Essential for Mosquito Transmission

摘要: Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin glutathione (GSH) that thought play a major role as antioxidants during stage infection. In this report, we analyzed critical component GSH biosynthesis pathway using reverse genetics. berghei parasites lacking expression gamma-glutamylcysteine synthetase (γ-GCS), rate limiting enzyme in de novo synthesis GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, γ-GCS is not essential for development. Despite significant reduction levels, forms pbggcs− showed only defect growth compared wild type. contrast, dramatic effect on development mosquito was observed. mosquitoes with resulted reduced numbers stunted oocysts did produce sporozoites. These results important implications design drugs aiming at interfering redox-system stages demonstrate pivotal mosquito.