salivary apyrase regulates blood meal hemostasis and drives malaria parasite transmission.

Mosquito salivary proteins play a crucial role in regulating hemostatic responses at the bite site during blood feeding. In this study, we investigate the function of salivary apyrase (AgApyrase) in transmission. Our results demonstrate that salivary apyrase interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protein previously shown to be required for transmission. Microscopy imaging shows that mosquitoes ingest a substantial amount of apyrase during blood feeding which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. Supplementation of infected blood with apyrase significantly enhanced infection in the mosquito midgut. In contrast, AgApyrase immunization inhibited mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for transmission to mosquitoes and to the mammal host, underscoring the potential for new strategies to prevent malaria transmission.