Disruption of mosquito physiology by targeting molecules involved in post-bloodmeal homeostasis

Mosquito molecules must be identified that can be used in novel antimosquito approaches. Here we report the combination of DNA immunization and reverse genetics to test the impact on mosquito physiology when molecules from Anopheles gambiae midgut were targeted immunologically and/or silenced. We selected molecules putatively involved in blood homeostasis in the mosquito, including peritrophic matrix (PM) formation, iron metabolism, and redox metabolism. There was a strong specific immune response elicited in mice immunized with a peritrophin cDNA. The mortality of mosquitoes fed on these mice varied, being significant in one experiment but not in another. Animals immunized with An. gambiae ferritins and laccase cDNAs did not mount an effective immune response against these proteins. Reverse genetics was performed through double-stranded RNA (dsRNA) injections to induce RNA interference (RNAi). Our results demonstrated there was higher lipid oxidation in mosquitoes that had ferritins, laccase, or thioredoxin transcripts silenced. Mosquito survival was significantly decreased when catalase and thioredoxin transcripts were silenced. Moreover, Plasmodium berghei development was likely affected in catalase and thioredoxin-silenced mosquitoes. We have found An. gambiae molecules that induce higher oxidative stress in the mosquitoes and that should be considered as targets in novel antimosquito strategies