Anopheles Coluzzii Stearoyl-Coa Desaturase Is Essential For Adult Female Survival And Reproduction Upon Blood Feeding

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne diseases.Author summary Female mosquitoes can become infected with malaria parasites upon ingestion of blood from an infected person and can transmit the disease when they bite another person some days later. The bloodmeal is rich in proteins which female mosquitoes use to develop their eggs after converting them first to saturated and then to unsaturated fatty acids inside their gut cells. Here, we present the characterization of the enzyme that mosquitoes use to convert saturated to unsaturated fatty acids and show that when this enzyme is eliminated or inhibited mosquitoes cannot produce eggs and die soon after they feed on blood. The mosquito death appears to be primarily associated with the collapse of their gut epithelial barrier due to the loss of cell membrane integrity, leading to their inner body cavity being filled with the ingested blood. These mosquitoes also suffer from an acute and detrimental auto-inflammatory condition due to mounting of a potent immune response in the absence of any infection. We conclude that this enzyme and the mechanism of converting blood-derived proteins to unsaturated fatty acids as a whole can be a good target of interventions aiming at limiting the mosquito abundance and blocking malaria transmission.