Mechanistic Elucidation of PxKir1‐Mediated Indoxacarb Resistance in Plutella xylostella: Implications for Insecticide Resistance Management and Sustainable Pest Control

ABSTRACT Field‐evolved indoxacarb resistance in many kinds of pests poses growing threats to pest management. Previous studies revealed that inward rectifier potassium channels ( PxKirs ) in Plutella xylostella are implicated in resistance mechanisms, but their functional roles remain uncharacterized. Here, we investigated a field‐derived strain (RR = 129.58) exhibiting significant downregulation of PxKir1 , PxKir2 , PxKir3A/B , and PxKir4 under LC 50 indoxacarb exposure. Tissue‐specific profiling revealed PxKir1 dominance in the head, while other isoforms enrichment in Malpighian tubules and midgut. RNAi‐mediated PxKir1 suppression unexpectedly increased resistance by 56.3%, demonstrating its counterintuitive regulatory role. Mechanistically, silencing reduced GST (9.4%) and P450 (31.8%) activities but elevated CarE activity (1.7‐fold), accompanied by downregulation of PxGSTO4 , PxNa v , and PxCYP6BF1v2 . Phenotypic analyses revealed multigenerational costs: prolonged pupal duration (4.7%), reduced pupal weight (17.6%) and length (3.9%), and shortened male longevity (13.8%) despite elevated eclosion rates (37.4%). Our findings establish PxKir1 as a dual‐function modulator governing indoxacarb resistance through (1) coordinated detoxification enzyme regulation and (2) life‐history trade‐offs favoring survival over developmental fitness. This study provides a comprehensive understanding of the role of PxKir1 in indoxacarb resistance and highlights the physiological, biochemical, and biological consequences of its silencing. The findings offer valuable insights for developing resistance management strategies, screening novel insecticidal agents, and optimizing the application of chemical insecticides to mitigate resistance development in P. xylostella populations.