Chemical Proteomics Reveals That Camptothecin Weakens Insect Immunity against Bacteria by Suppressing Antimicrobial Peptide Expression

Plant natural products are crucial in defending against herbivorous insects and are widely used in pest control, yet their mechanisms remain complex and insufficiently studied. This study employed a reverse strategy to investigate the mechanism of camptothecin (CPT), a botanical pesticide. By using a CPT-based chemical probe coupled with proteomic analysis, immune-related proteins, including those involved in prophenoloxidase (PPO) activation and antimicrobial peptide (AMP) synthesis, were identified in the Asian corn borer, <i>Ostrinia furnacalis</i>. The findings demonstrated that CPT weakens insect immunity, primarily by inhibiting AMP synthesis rather than affecting PPO activation. Specifically, CPT downregulated the expression of genes in the IMD pathway and those encoding AMPs (attacin and gloverin). Additionally, CPT-fed insects exhibited reduced antibacterial activity. This research uncovers a novel mechanism of CPT as an insect immunosuppressant, offering new insights that may enhance the application of CPT in pest control.