Final Report Summary - ANOREP (Targeting the reproductive biology of the malaria mosquito Anopheles gambiae: from laboratory studies to field applications)
Despite recent progress in combating the malaria parasite, nearly 200 million people are infected and around 500,000 deaths are recorded every year, mostly young children in sub-Saharan Africa. Widespread insecticide resistance among Anopheles mosquito populations represents one of the most significant threats to existing malaria interventions, and available tools are unlikely to sustain current control levels let alone achieve elimination. Compounds that disrupt the reproductive biology and behavior of female anophelines offer new approaches to reducing mosquito populations and malaria prevalence.
In this project, we have identified male and female factors that play key roles in shaping the reproductive success of Anopheles gambiae mosquitoes, the major vectors of malaria. Specifically, our studies have determined that in An. gambiae as well as in other important anopheline vector species, sexual transfer of the steroid hormone 20-hydroxyecdysone (20E) by the male induces a dramatic series of molecular events in the female that culminate in increased oogenesis, induction of egg laying and loss of the female’s susceptibility to further mating. In depth studies have unraveled the molecular interactions between this male hormone and female proteins induced by copulation that are crucial to the fecundity (via the function of the female protein Mating induced Stimulator of Oogenesis, MISO) and fertility (through the activity of the Heme Peroxidase HPX15) of these mosquitoes. Mechanisms of sperm viability have been identified and can now be targeted to induce sterility. These are the first example of male-female reproductive partnerships in An. gambiae, and the molecular pathways triggered by these interactions are good targets for future vector control strategies aimed at suppressing field mosquito populations.
Moreover, we have developed and tested tools for field applications aimed at mosquito control. 20E-agonists have been validated as mosquito control agents to stop disease transmission. After application to females, these 20E agonistic compounds (named dibenzoylhydrazines, DBHs) prevent virgin females from mating, completely block egg development, and stop Plasmodium falciparum parasites from developing in the mosquito vector. When these effects are modeled, we see that the use of DBH in mosquito nets or indoor sprays would have a strong impact on malaria transmission dynamics.
Overall this study significantly increases knowledge of molecular pathways crucial for mosquito reproductive fitness and generates new promising tools for the control of malaria parasites.
In this project, we have identified male and female factors that play key roles in shaping the reproductive success of Anopheles gambiae mosquitoes, the major vectors of malaria. Specifically, our studies have determined that in An. gambiae as well as in other important anopheline vector species, sexual transfer of the steroid hormone 20-hydroxyecdysone (20E) by the male induces a dramatic series of molecular events in the female that culminate in increased oogenesis, induction of egg laying and loss of the female’s susceptibility to further mating. In depth studies have unraveled the molecular interactions between this male hormone and female proteins induced by copulation that are crucial to the fecundity (via the function of the female protein Mating induced Stimulator of Oogenesis, MISO) and fertility (through the activity of the Heme Peroxidase HPX15) of these mosquitoes. Mechanisms of sperm viability have been identified and can now be targeted to induce sterility. These are the first example of male-female reproductive partnerships in An. gambiae, and the molecular pathways triggered by these interactions are good targets for future vector control strategies aimed at suppressing field mosquito populations.
Moreover, we have developed and tested tools for field applications aimed at mosquito control. 20E-agonists have been validated as mosquito control agents to stop disease transmission. After application to females, these 20E agonistic compounds (named dibenzoylhydrazines, DBHs) prevent virgin females from mating, completely block egg development, and stop Plasmodium falciparum parasites from developing in the mosquito vector. When these effects are modeled, we see that the use of DBH in mosquito nets or indoor sprays would have a strong impact on malaria transmission dynamics.
Overall this study significantly increases knowledge of molecular pathways crucial for mosquito reproductive fitness and generates new promising tools for the control of malaria parasites.