Ferroptotic cyanobacteria as biocontrol agent of the southern house mosquito Culex quinquefasciatus

Culex quinquefasciatus is a hematophagous mosquito, widely distributed around the world, that plays a crucial role in public and veterinary health. As an efficient vector of etiological agents, it exhibits a marked preference for urban environments and human blood. Despite advances in mosquito-borne disease control, managing mosquito populations remains an economically efficient and safe strategy to reduce the impact of epidemic outbreaks. However, achieving this goal requires ecologically acceptable tools that ensure sustainability and minimize adverse environmental impacts. In the present work, we investigated the effect of a non-toxigenic model cyanobacterium on Cx. quinquefasciatus larvae through regulated cell death. We observed that heat stress treatment of Synechocystis PCC 6803 inducing ferroptosis, results in larval lipid oxidation, leading to their death. This effect can be mitigated by rearing larvae in an environment containing canonical inhibitors of ferroptosis, such as ferrostatin 1, or antioxidants, like glutathione and ascorbic acid. Furthermore, larval cell death induced by ferroptotic cyanobacteria is closely linked to oxidative dysregulation and lipid peroxidation, both hallmarks of ferroptosis. Moreover, while ferroptotic Synechocystis significantly affects larval development, it does not influence oviposition site selection by gravid females.