Molecular basis of polyphagy: The detoxification gene <i>HcGST18</i> underlies host plant adaptation in the <i>Hyphantria cunea</i>

A broad host range facilitates the rapid spread of Hyphantria cunea. This study explored the mechanism underlying the multi-host adaptability of H. cunea larvae, focusing on glutathione S-transferase (GST), and developed nucleic acid pesticides targeting key GST genes to disrupt larval adaptability. The results revealed that GST enzyme activity in H. cunea larvae is specifically responsive to host plants. Inhibition of GST enzyme activity significantly reduced larval body weight and food consumption across various host plant groups. qPCR analysis demonstrated differential expression patterns of GST family genes in response to different host plants, with HcGST18 showing the highest expression in moderately and less preferred host plant groups. Silencing HcGST18 significantly reduced larval body weight across all host plant groups and increased cumulative mortality in moderately and less preferred host plant groups. Further validation confirmed that transgenic Drosophila and Sf9 cells overexpressing HcGST18 exhibited significantly reduced sensitivity to the plant secondary metabolites coumarin and cytisine. Additionally, a nucleic acid pesticide targeting HcGST18, CS-dsHcGST18, was developed using the natural nanomaterial chitosan (CS). CS effectively protected dsHcGST18 from degradation by H. cunea larval gut fluid. Treatment with CS-dsHcGST18 significantly reduced weight of H. cunea larvae after feeding on different hosts, but there was no significant change in mortality. In addition, Treatment with CS-dsHcGST18 treatment significantly increased larval sensitivity to plant secondary metabolites (coumarin). In conclusion, HcGST18 is a key detoxification gene mediating the multi-host adaptability of H. cunea.