title: Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes.
abstract: 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, is a surface-associated molecule which is important in sporozoite infectivity to the host. 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.
authors.affiliation: Michael Heidelberger Division of Immunology, Department of Pathology, Kaplan Cancer Center, New York University Medical Center, 10016, USA. menarr01@mcrcr6.med.nyu.edu
authors.forename: R
authors.initials: R
authors.lastname: Ménard
authors.forename: A A
authors.initials: AA
authors.lastname: Sultan
authors.forename: C
authors.initials: C
authors.lastname: Cortes
authors.forename: R
authors.initials: R
authors.lastname: Altszuler
authors.forename: M R
authors.initials: MR
authors.lastname: van Dijk
authors.forename: C J
authors.initials: CJ
authors.lastname: Janse
authors.forename: A P
authors.initials: AP
authors.lastname: Waters
authors.forename: R S
authors.initials: RS
authors.lastname: Nussenzweig
authors.forename: V
authors.initials: V
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D018390:Gene Targeting; D007305:Insecticide Resistance / Q000235:genetics; D009097:Multienzyme Complexes / Q000235:genetics; D010957:Plasmids; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D012469:Salivary Glands / Q000469:parasitology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics
chemical_list: D009097:Multienzyme Complexes; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase