Host EV–derived lipids promote malaria parasite development via mosquito fatty acid β-oxidation

Malaria parasites must transition between mammals and mosquitoes, but how they adapt to such distinct environments is unclear. We show that blood from infected mammals buffers this environmental shift by packaging parasite-induced signals into extracellular vesicles (EVs). EVs internalized by mosquito midgut increases expression of VLCAD and raises levels of a 22-carbon fatty acid, driving fatty acid breakdown and acetyl-CoA production. The parasite exploits this metabolic shift to synthesize its own lipids during oocyst growth. Stable isotope tracing confirmed that ¹³ C ₄ -labelled behenic acid is degraded and incorporated into parasite fatty acids. Lipidomic profiling further revealed that ceramides enriched in the EVs are key mediators. These findings identify a mechanism by which host bood-derived EVs reprogram mosquito lipid metabolism to promote parasite transmission.