Pantothenate regulates feeding and reproduction in the malaria vector Anopheles stephensi, with patterns dependent on supplementation scheme and parental nutrition

Background: Pantothenate (Pan), or vitamin B5, is the substrate for biosynthesis of coenzyme A (CoA), an essential cellular cofactor involved in many metabolic processes. Our previous studies demonstrated that Pan availability influences a broad range of traits across multiple species, including malaria parasite development in the mosquito Anopheles stephensi. Accordingly, restricting Pan availability during parasite development may be a viable strategy for malaria control. However, the physiological roles of Pan in A. stephensi remain unclear. In these studies, we investigated the effects of Pan supplementation on this globally important malaria vector. Methods: Female A. stephensi were supplemented with Pan via either water, which, similar to plant nectar, is directed to the crop and then slowly released into the midgut, or blood, which transits directly to the midgut for digestion. The effects of provisioning on subsequent blood feeding behavior, reproduction, and offspring sex ratio were assessed. We evaluated these traits across multiple generations, with and without additional supplementation of offspring. Results: Our findings revealed that Pan regulates vectorially important traits in concentration-, delivery-, and age-dependent ways. The greatest effects of Pan provisioning were on reproduction. The unsupplemented offspring of mothers supplemented with Pan via water exhibited increased fecundity, indicating transgenerational effects from supplemented mothers. However, when Pan was provisioned in blood, only mothers and their supplemented offspring exhibited altered reproduction. Conclusions: Our work establishes the importance of Pan in A. stephensi reproduction and provides a foundation for investigating the transgenerational effects of Pan and CoA on mosquito physiology. These observations suggest that targeting Pan-CoA biology in Anopheles spp. could provide opportunities for novel mosquito control strategies.