The mosquitoAnopheles stephensilimits malaria parasite development with inducible synthesis of nitric oxide

• DOI: 10.1073/pnas.95.10.5700
• Publication Date: 2002-07-26T14:40:11Z
• Authors: Shirley Luckhart; Yoram Vodovotz; Liwang Cui; Ronald Rosenberg
• Keywords: 0301 basic medicine; Plasmodium berghei; Molecular Sequence Data; Plasmodium falciparum; Nitric Oxide Synthase Type II; Arginine; Nitric Oxide; 3. Good health; 03 medical and health sciences; Enzyme Induction; Hemolymph; Anopheles; Animals; Humans; Amino Acid Sequence; Nitric Oxide Synthase

We have discovered that the mosquitoAnopheles stephensi, a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (NO). Elevated expression ofA. stephensiNO synthase (NOS), which is highly homologous to characterized NOS genes, was detected in the midgut and carcass soon after invasion of the midgut byPlasmodium. Early induction is likely primed by bacterial growth in the blood meal. Later increases inA. stephensiNOS expression and enzyme activity occurred at the beginning of sporozoite release. Circulating levels of nitrite/nitrate, end-products of NO synthesis, were significantly higher inPlasmodium-infected mosquitoes. Dietary provision of the NOS substratel-arginine reducedPlasmodiuminfections inA. stephensi. In contrast, dietary provision of a NOS inhibitor significantly increased parasite numbers in infected mosquitoes, confirming thatA. stephensilimitsPlasmodiumdevelopment with NO.