THE MOSQUITO ANOPHELES-STEPHENSI LIMITS MALARIA PARASITE DEVELOPMENT WITH INDUCIBLE SYNTHESIS OF NITRIC-OXIDE

We have discovered that the mosquito Anopheles stephensi, a natural ve ctor of human malaria, limits parasite development with inducible synt hesis of nitric oxide (NO), Elevated expression of A. stephensi NO syn thase (NOS), which is highly homologous to characterized NOS genes, wa s detected in the midgut and carcass soon after invasion of the midgut by Plasmodium, Early induction is likely primed by bacterial growth i n the blood meal. Later increases in A. stephensi NOS expression and e nzyme activity occurred at the beginning of sporozoite release. Circul ating levels of nitrite/nitrate, end-products of NO synthesis, were si gnificantly higher in Plasmodium-infected mosquitoes. Dietary provisio n of the NOS substrate L-arginine reduced Plasmodium infections in A. stephensi. In contrast, dietary provision of a NOS inhibitor significa ntly increased parasite numbers in infected mosquitoes, confirming tha t A. stephensi limits Plasmodium development with NO.