Metabolic balancing by miR-276 shapes the mosquito reproductive cycle and Plasmodium falciparum development

Abstract

Anopheles mosquitoes are obligate vectors of the human malaria parasite Plasmodium falciparum. The blood-feeding behavior of Anopheles females delivers essential nutrients for egg development and drives transmission from one human host to another. Plasmodium growth is adapted to the vector reproductive cycle, but how changes in the reproductive cycle impact parasite development is poorly understood. Here, we show that the blood meal-induced miR-276-5p fine-tunes the duration of the mosquito reproductive cycle. Silencing of miR-276 prolonged amino acid catabolism and increased female fertility rates, suggesting that timely termination of the reproductive cycle restricts mosquito investment into reproduction. Prolongation of the reproductive period in P. falciparum-infected females compromised the development of the transmissible parasite form called sporozoite. Our results suggest that Plasmodium sporogony exploits surplus resources after mosquito reproductive investment and demonstrate the crucial role of the mosquito amino acid metabolism in parasite within-vector proliferation and malaria transmission.