Non-competitive resource exploitation within-mosquito shapes evolution of malaria virulence

Malaria is a fatal human parasitic disease transmitted by a mosquito vector. The evolution of within-host malaria virulence has been the focus of many empirical and theoretical studies. However, the vectors contribution to virulence evolution is not well understood. Here we explored how within-vector resource exploitation impacts evolutionary trajectories of within-host Plasmodium virulence. We developed a nested model of within-vector dynamics and malaria epidemiology, which predicted that non-competitive resource exploitation within-vector restricts within-host parasite virulence. To validate our model, we experimentally manipulated mosquito lipid trafficking and gauged within-vector parasite development, within-host infectivity and virulence. We found that mosquito-derived lipids determine within-host parasite virulence by shaping development and metabolic activity of transmissible sporozoites. Our findings uncover the role of within-vector environment in regulating within-host Plasmodium virulence and identify Plasmodium metabolic traits that may contribute to the evolution of malaria virulence.