Predictive chemoproteomics and functional validation reveal Coeae6g mediated insecticide cross-resistance in the malaria vector Anopheles gambiae

This project investigates insecticide resistance mechanisms in Anopheles gambiae using Activity-Based Protein Profiling (ABPP). By targeting serine hydrolases (SHs) with fluorophosphonate (FP) probes and mass spectrometry, we identified COEAE6G as a key enzyme conferring resistance to Pirimiphos-methyl (PM) and cross-resistance to other insecticides. Functional validation, including recombinant protein assays and transgenic mosquito lines, confirmed COEAE6G's role in resistance. This work provides valuable insights into resistance mechanisms, aiding the development of sustainable malaria vector control strategies.