The E205D mutation in CYP6P3 drives pyrethroid insecticide resistance in the African malaria mosquito vector Anopheles gambiae

Deciphering the molecular drivers of insecticide resistance is paramount to extending the effectiveness of malaria vector control tools. Here, we demonstrate that a P450 haplotype spanning a Glu 205 →Asp (E205D) amino acid point mutation in the CYP6P3 gene drives pyrethroid insecticide resistance in the mosquito malaria vector Anopheles gambiae . Pooled whole-genome DNA sequencing data from A. gambiae mosquitoes detected a major P450-linked locus (CYP6 haplotype) on chromosome 2R adjacent to the locus encoding a sodium channel. In vitro metabolism assays with recombinantly expressed CYP6P3 protein revealed that the catalytic efficiency of the 205D variant for the pyrethroid insecticide permethrin was 3.7 times…