Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes

Malaria parasites undergo a sporogonic cycle in the mosquito vector. Sporozoites, the form of the parasite injected into the host during a bloodmeal, develop inside oocysts in the insect midgut, then migrate to and eventually invade the salivary glands. The circumsporozoite protein (CS), one of the major proteins synthesized by salivary gland sporozoites 1 , is a surface-associated molecule which is important in sporozoite infectivity to the host 2 . Here, by gene targeting, we created Plasmodium berghei lines in which the single-copy CS gene was disrupted. The CS( − ) and wild-type parasites produced similar numbers of oocysts of comparable size in the mosquito midgut. In the CS( − ) oocysts, however, sporozoite formation was profoundly inhibited. CS therefore appears to have a pleiotropic role and to be vital for malaria parasites in both the vector and the host: in mosquitoes, CS is essential for sporozoite development within oocysts, and in the vertebrate host it promotes sporozoite attachment to hepatocytes 3–7 .