Transgenic CncC overexpression confers low-level but broad-spectrum insecticide resistance in Plutella xylostella

The transcription factor CncC is a central regulator of xenobiotic adaptation in insects. Although its upregulation is frequently associated with insecticide resistance, the specific in vivo function and the physiological costs associated with its constitutive activation remain unclear. Initial observations in a field population (KM24) of Plutella xylostella (L.) revealed that multi-insecticide resistance was accompanied by elevated CncC expression. To functionally test the contribution of CncC, a piggyBac-mediated transgenic strain overexpressing CncC by approximately 200-fold was established. This strain exhibited low-level broad-spectrum insecticide resistance (2.6- to 4.3-fold), accompanied by the upregulation of multiple detoxification genes as revealed by transcriptomic analysis. However, this manipulation conferred a significant fitness cost, characterized by prolonged larval development, decreased pupal mass, and reduced fecundity. Subsequent investigation revealed CncC activation suppressed the key juvenile hormone (JH) biosynthetic gene JHAMT while inducing the degrading genes JHE and JHEH, resulting in a marked reduction in larvae JH III titers. These findings provide direct in vivo evidence that constitutive CncC activation alone yields limited resistance while disrupting hormonal homeostasis, imposing profound physiological penalties. This study not only elucidates the contribution of CncC upregulation to insecticide resistance but also suggests that targeting the CncC-JH axis could be a viable strategy for resistance management.