RT Journal Article SR Electronic T1 Mosquito lipids regulate Plasmodium sporogony and infectivity to the mammalian host JF bioRxiv FD Cold Spring Harbor Laboratory SP 149443 DO 10.1101/149443 A1 Giulia Costa A1 Maarten Eldering A1 Randall L. Lindquist A1 Anja E. Hauser A1 Robert Sauerwein A1 Christian Goosmann A1 Volker Brinkmann A1 Elena A. Levashina YR 2017 UL http://biorxiv.org/content/early/2017/06/13/149443.abstract AB Malaria is a human parasitic disease that is transmitted by a mosquito vector. Plasmodium parasites, the causative agents, differ in their infectivity and virulence to the mammalian host, but the mechanistic underpinnings of this variation remain unknown. As mosquitoes provide a nutrient-rich niche for development of transmissible stages, we examined the role of lipids in parasite development and infectivity by disrupting lipid trafficking in mosquito adults. We show that depleting the major mosquito lipoprotein lipophorin deprives parasites of neutral lipids, arrests oocysts growth and impairs sporozoite formation. Importantly, lipid deficiency decreases parasite mitochondrial membrane potential and severely compromises sporozoite infectivity and virulence in the mammalian host. Our findings demonstrate the requirement of mosquito lipids for Plasmodium metabolism, and uncover the mitochondrial contribution to parasite infectivity and virulence. By drawing a connection between vector nutrition and malaria virulence, our results redefine the paradigm of vector-host-pathogen interactions.