Arginine kinase 2 knockdown enhances deltamethrin sensitivity in Aedes aegypti

The mosquito Aedes aegypti is the main vector of the etiological agents of dengue, Zika, and chikungunya representing major public health concern in tropical and subtropical regions. Control of A. aegypti relies mainly on pyrethroid insecticides such as deltamethrin, but increasing resistance has reduced their effectiveness. Here, we identified and characterized two arginine kinase genes (ak1 and ak2) in A. aegypti, a key enzyme involved in regulating energy homeostasis in insects and investigated their contribution to insecticide tolerance. We performed protein phylogenetic analysis and protein expression profiling by Western blot assay. Transcript profiling revealed distinct developmental and tissue-specific expression patterns, with both genes highly expressed in the head. Deltamethrin exposure induced oxidative stress and ATP depletion, accompanied by a marked upregulation of ak2, but not ak1. RNA interference-mediated silencing of ak2 in third instar larvae significantly reduced pupal survival under deltamethrin treatment, while ak1 knockdown had no effect. These results indicate that ak2 plays a role in mediating tolerance to chemical stress in A. aegypti, likely through the maintenance of ATP homeostasis during oxidative stress. Our findings identify ak2 as a promising molecular target for innovative vector control strategies, including RNAi-based approaches or the development of small-molecule inhibitors that potentiate the efficacy of pyrethroid insecticides.