Abstract

Spodoptera frugiperda (fall armyworm) is a globally distributed and highly destructive migratory pest, while Serratia marcescens is a widespread entomopathogenic bacterium capable of infecting diverse insects. In this study, oral infection with S. marcescens strain SM001 exhibited potent virulence, with an LC 50 of 7.40 × 10 6 CFU/mL at 168 h post-infection (hpi). Logistic regression modeling demonstrated that the bacterium enters an exponential proliferation phase within the hemolymph approximately 48–54 h after infection. Infection significantly upregulated Duox and Nos , induced severe oxidative stress, and activated an apoptotic cascade involving Cyt c , p53 , and caspase , culminating in extensive midgut epithelial cell apoptosis. Mitigating oxidative stress via targeted Vitamin C supplementation or Duox knockdown alleviated midgut tissue damage and delayed bacterial dissemination. However, exogenous Vitamin C treatment decreased larval mortality, whereas Duox knockdown failed to improve overall survival, revealing a critical physiological trade-off between ROS-mediated pathogen clearance and host immunopathology. Overall, SM001 disrupts midgut redox homeostasis, drives excessive H 2 O 2 accumulation, and breaches the intestinal barrier to facilitate hemocoel translocation, ultimately leading to lethal systemic septicemia. These findings highlight the pivotal role of host-mediated immunopathology in bacterial pathogenesis and provide a robust theoretical foundation for developing advanced microbial control strategies against S. frugiperda .