Functional characterization of two delta-class glutathione S-transferases genes in detoxifying acaricides in...

Scabies (or Sarcoptic mange) is a highly contagious skin disease caused by the ectoparasite Sarcoptes scabiei. The resistance of S. scabiei to common acaricides like permethrin has been reported, yet their precise mechanisms remain elusive. Glutathione S-Transferase (GSTs) constitute an important class of detoxification enzymes. In this study, we found that the expression levels of SsGSTd3 and SsGSTd5 in S. scabiei were significantly up-regulated after exposure to LC₃₀ of permethrin, amitraz, and selamectin, suggesting that SsGSTd3 and SsGSTd5 are involved in the detoxification of these acaricides. Therefore, we used in vitro metabolic assay and bacterial survival assays to further investigate their specific detoxification mechanisms. Co-incubation with the acaricides reduced the 1-Chloro-2,4-dinitrobenzene (CDNB) activities of both recombinant proteins to varying degrees. HPLC analysis revealed that SsGSTd3 and SsGSTd5 metabolized 35.24% and 53.28% of permethrin, respectively, but did not metabolize amitraz. SsGSTd3 metabolized a small fraction of selamectin (3.25%). In addition, bacterial survival assays demonstrated that under oxidative stress induced by CHP and H₂O₂, the OD₆₀₀ values of E. coli overexpressing SsGSTd3 or SsGSTd5 were significantly higher than those of control group, indicating robust antioxidant activity for both proteins. In conclusion, our findings demonstrate that SsGSTd3 and SsGSTd5 facilitate permethrin detoxification via a dual mechanism-metabolic and alleviation of oxidative stress, and may represent an early warning sign of decreased susceptibility to amitraz and selamectin through their antioxidant functions.