Avian malaria and the overlooked metabolic pathways underlying mosquito-Plasmodium interactions

Avian malaria parasites pose a significant threat to conservation, affecting populations worldwide. Despite this, our understanding of factors influencing the transmission of avian Plasmodium parasites by vectors is limited to the study of mosquito immune responses. However, the complex life cycle of Plasmodium within the vector suggests that non-immune physiological and metabolic pathways may play equally, if not more, crucial roles in determining whether the parasite completes its development and successfully transmits to the next host. We review some of these pathways, uncovering a fragmented and contradictory body of knowledge. Through transcriptomic analysis of infected and uninfected mosquitoes at various stages of infection, we identify differential expression of numerous metabolic pathways that are essential for Plasmodium development. These include genes involved in meeting the parasite's energetic needs, digestive enzymes facilitating midgut barrier traversal, and salivary enzymes enabling blood meal uptake, among others. This suggests that the parasite has evolved mechanisms to modulate these pathways, thereby enhancing and prolonging infection and transmission. Our findings emphasize the need for a broader, integrative approach to better understand the reciprocal selective pressures between malaria parasites and their vectors and to find novel targets for controlling parasite transmission and ultimately improving malaria control strategies.