The ecdysone receptor regulates several key physiological factors in Anopheles funestus.

BACKGROUND: Malaria is a devastating disease, transmitted by female Anopheles mosquitoes infected with Plasmodium parasites. Current insecticide-based strategies exist to control the spread of malaria by targeting vectors. However, the increase in insecticide resistance in vector populations hinder the efficacy of these methods. It is, therefore, essential to develop novel vector control methods that efficiently target transmission reducing factors such as vector density and competence. A possible vector control candidate gene, the ecdysone receptor, regulates longevity, reproduction, immunity and other physiological processes in several insects, including malaria vectors. Anopheles funestus is a prominent vector in sub-Saharan Africa, however, the function of the ecdysone receptor in this mosquito has not previously been studied. This study aimed to determine if the ecdysone receptor depletion impacts An. funestus longevity, reproduction and susceptibility to Plasmodium falciparum infection. METHODS: RNA interference was used to reduce ecdysone receptor expression levels in An. funestus females and investigate how the above-mentioned phenotypes are influenced. Additionally, the expression levels of the ecdysone receptor, and reproduction genes lipophorin and vitellogenin receptor as well as the immune gene, leucine rich immune molecule 9 were determined in ecdysone receptor-depleted mosquitoes using quantitative polymerase chain reaction. RESULTS: Ecdysone receptor-depleted mosquitoes had a shorter lifespan, impaired oogenesis, were less fertile, and had reduced P. falciparum infection intensity. CONCLUSIONS: Overall, this study provides the first experimental evidence that supports ecdysone receptor as a potential target in the development of vector control measures targeting An. funestus.

20-Hydroxyecdysone (20E) signaling as a promising target for the chemical control of malaria vectors.

With the rapid development and spread of resistance to insecticides among anopheline malaria vectors, the efficacy of current World Health Organization (WHO)-approved insecticides targeting these vectors is under threat. This has led to the development of novel interventions, including improved and enhanced insecticide formulations with new targets or synergists or with added sterilants and/or antimalarials, among others. To date, several studies in mosquitoes have revealed that the 20-hydroxyecdysone (20E) signaling pathway regulates both vector abundance and competence, two parameters that influence malaria transmission. Therefore, insecticides which target 20E signaling (e.g. methoxyfenozide and halofenozide) may be an asset for malaria vector control. While such insecticides are already commercially available for lepidopteran and coleopteran pests, they still need to be approved by the WHO for malaria vector control programs. Until recently, chemicals targeting 20E signaling were considered to be insect growth regulators, and their effect was mostly studied against immature mosquito stages. However, in the last few years, promising results have been obtained by applying methoxyfenozide or halofenozide (two compounds that boost 20E signaling) to Anopheles populations at different phases of their life-cycle. In addition, preliminary studies suggest that methoxyfenozide resistance is unstable, causing the insects substantial fitness costs, thereby potentially circumventing one of the biggest challenges faced by current vector control efforts. In this review, we first describe the 20E signaling pathway in mosquitoes and then summarize the mechanisms whereby 20E signaling regulates the physiological processes associated with vector competence and vector abundance. Finally, we discuss the potential of using chemicals targeting 20E signaling to control malaria vectors.