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Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite  Plasmodium berghei  has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for  P. berghei  female gamete fertility, is shown to serve a different function in  Plasmodium falciparum , protecting ookinetes from the mosquito immune response. Here, we investigate the function of  P. berghei  P47 in  Anopheles gambiae  mosquito infections. We show that P47 is expressed on the surface of both female gametocytes and ookinetes where it serves distinct functions in promoting gametocyte-to-ookinete development and protecting ookinetes from the mosquito complement-like response, respectively. The latter function is essential, as ookinetes lacking P47 are targeted for killing while traversing the mosquito midgut cells and eliminated upon exposure to hemolymph proteins of the complement-like system. Silencing key factors of the complement-like system restores oocyst development and disease transmission to rodent hosts. Our data establish a dual role of  P. berghei  P47  in vivo  and reinforce the use of this parasite to study the impact of the mosquito immune response on human malaria transmission.

Plasmodium berghei P47 is essential for ookinete protection from the Anopheles gambiae complement-like response