ASTMH 2016, Maurice A. Itoe: “Elucidating the role of lipogenic and lipolytic pathways in mosquito reproduction and P. falciparum transmission”

In collaboration with ASTMH, Image Audiovisuals, and session presenters, MESA brings you this webcast from the 65th ASTMH annual meeting in Atlanta, November 2016.

Title: “Elucidating the role of lipogenic and lipolytic pathways in mosquito reproduction and P. falciparum transmission”

Speaker: Maurice A. Itoe, Harvard T.H. Chan School of Public Health

Session information: Scientific Session 130: “Mosquitoes: Biochemistry and Molecular Biology”

Wednesday, 16 November, 10:15am – 12:00pm, Marriott – Room A706 / A707

Abstract:

Female Anopheles mosquitoes undergo a number of blood feeding cycles on a vertebrate host in order to produce multiple egg batches, and these obligatory steps in the mosquito life cycle are exploited by Plasmodium parasites for their own transmission. Blood feeding is therefore a key step for both mosquito reproduction and parasite transmission. Indeed these two processes are temporally and physiologically coupled and can be exploited to impact malaria dynamics in endemic areas. Previous studies revealed a correlation between blood meal digestion and major changes in transcriptional profiles of metabolic genes involved in lipid biosynthesis, transport, and breakdown, suggesting the occurrence of de novo lipid synthesis triggered by blood feeding followed by lipid mobilization. Here, we aim to elucidate the specific role of blood meal-derived lipids (and/or of lipids synthesized de novo after a blood meal) in Anopheles reproduction and parasite development in mosquito stages. To address this, we performed targeted depletion of key lipogenic and lipolytic enzymes in the main African malaria vector using RNA interference (RNAi) and assessed their impact on oogenesis and P. falciparum infection. Strikingly, knockdown of acetyl-CoA carboxylase (ACC), one of the rate-limiting enzymes in de novo fatty acid synthesis (lipogenesis), reduced egg development and P. falciparum infection in An. gambiae. On the other hand, inhibition of triglyceride (TAG)-lipase, involved in lipolytic breakdown of TAGs to yield free fatty acids and diacylglycerol (DAG), had opposing effects on egg development and Plasmodium infection: depletion of TAG-lipase significantly impaired the number of eggs developed but resulted in a significant increase in oocyst size without any apparent impact on the number of oocysts per midgut. The latter results suggest occurrence of possible scavenging of host TAGs by malaria parasites to meet developmental needs within the Anopheles vector. While further characterization is underway, these data provide the first direct evidence of the requirement of host lipids by human malaria parasites for successful transmission.