Activiation of the nitric oxide cycle by citrulline and arginine restores susceptibility of resistant brown planthoppers to the insecticide imidacloprid

Pest management, which is critical for global crop productivity, is hampered by rapidly evolving insecticide resistance in insect pests. The ability to manage the development of insecticide resistance is thus vital. Nitric oxide (NO) is a ubiquitous signaling molecule with important functions in a variety of biological processes. Here we show that imidacloprid-resistant brown planthoppers (BPH) are deficient in citrulline and arginine, both of which are involved in NO production, but exogenous citrulline and arginine render resistant BPH vulnerable to imidacloprid. BPH insecticide resistance results from low NO production; exogenous arginine and citrulline augment the NO signaling in BPH, leading to downregulation of CYP6AY1 and CYP6ER1, the cytochrome P450 s that contribute to imidacloprid detoxification, thereby restoring susceptibility. Two amino acids that can be used to restore susceptibility in insecticide-resistant insects are identified, establishing a novel metabolome-based approach for killing insecticide-resistant pests and providing a useful template for managing insecticide resistance.