PT  - JOURNAL ARTICLE
AU  - Giulia Costa
AU  - Maarten Eldering
AU  - Randall L. Lindquist
AU  - Anja E. Hauser
AU  - Robert Sauerwein
AU  - Christian Goosmann
AU  - Volker Brinkmann
AU  - Elena A. Levashina
TI  - Mosquito lipids regulate <em>Plasmodium</em> sporogony and infectivity to the mammalian host
AID  - 10.1101/149443
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 149443
4099  - http://biorxiv.org/content/early/2017/06/13/149443.short
4100  - http://biorxiv.org/content/early/2017/06/13/149443.full
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.