Mosquito metabolism shapes life-cycle strategies of Plasmodium parasites

The life-history of multicellular organisms is a collection of traits determining fitness described by growth, survival, and reproduction. Within-host survival and between-host transmission are key life-history traits of single-celled malaria parasites. Therefore, understanding the evolutionary forces that shape these components is crucial to predict malaria epidemiology, drug resistance, and virulence. The evolutionary strategies of Plasmodium parasites have been largely investigated in the vertebrate host. In contrast, very little is known about their adaptation strategies in the mosquito vector, possibly due to the experimental challenges encountered while studying vector-parasite interactions. Mathematical models offer a unique tool to study such complex biological systems, and have been extensively employed in malaria epidemiology. However, all models developed so far do not consider mosquito physiology. Here, we examine the life-history evolution of Plasmodium parasites with a novel individual-based model of malaria transmission that includes mosquito metabolism. Specifically, we model the metabolic cascade of resource allocation induced by blood-feeding, as well as the influence of multiple blood meals on parasite development. Our model shows that successful vector-to-human transmission events are rare, and are caused by long-lived mosquitoes. Interestingly, we observe that the life-history strategies of malaria parasites depend on the mosquito metabolic status. In our model, additional resources provided by multiple blood meals benefit selection for parasites with slow or intermediate developmental time. These results challenge the current concept that evolution selects for fast developing parasites to maximize their chances to complete their within-mosquito life cycle. We propose that the long sporogonic cycle observed for Plasmodium is not a constraint but rather an adaptation to increase transmission potential.