Controlling malaria mosquito reproduction via the octopamine beta2 receptor

Mosquito reproduction in a broad sense involves multiple steps from acoustic recognition of mating partners to egg hatching. We show that the octopamine receptor AgOctβ2R controls different aspects of this process in a sexually dimorphic manner. AgOctβ2R knockout males present auditory defects that impair their ability to inseminate females, whilst knockout females are sterile. These phenotypes suggest AgOctβ2R as a target to impair mosquito reproduction at multiple levels. We test the reproductive effects of the insecticide amitraz, an AgOctβ2R agonist, showing that amitraz exposure reduces insemination in the lab but not in the field and has no effects on female sterility, excluding its applicability as a mating disruptor. Pharmacological assays reveal that AgOctβ2R sensitivity to amitraz is reduced compared to other arthropods, but its responses can be altered by modifying residues in the binding pocket. Together, our results establish AgOctβ2R as a promising target to disrupt mosquito reproduction but emphasize the necessity of developing new tools to exploit this approach.