biostudies-literatureUnknown26(1)Tekoh TAMetabolic resistance to pyrethroids driven by cytochrome P450s is threatening malaria control interventions and may provide cross-resistance to insecticides with unrelated modes of action. Here, we show that cytochrome P450 genes CYP6P9a/b associated with pyrethroid resistance in Anopheles funestus also confer cross-resistance to a novel mitochondrial complex I inhibitor insecticide, code-named Sherlock. Using standard bioassays (CDC bottle bioassays, WHO cone bioassays, and WHO tunnel tests), the Sherlock and pyrethroid insecticides were tested against pyrethroid-resistant An. gambiae s.s. (Nkolondom, Cameroon) and An. funestus s.s. (Mibellon, Cameroon) and FUMOZ-R). Molecular assays (genotyping of P450 markers and qRT-PCR expression) were performed to investigate the underlying resistancBMC genomics837https://www.ebi.ac.uk/biostudies/studies/S-EPMC12465288biostudies-literatureThe duplicated cytochrome P450 CYP6P9a/b confers cross-resistance to a mitochondrial complex I inhibitor in the African malaria vector Anopheles funestus.PMC12465288Tekoh TATchouakui MSmall GMenze BTchapga WWondji MMugenzi LMJWondji CSfalseThe duplicated cytochrome P450 CYP6P9a/b confers cross-resistance to a mitochondrial complex I inhibitor in the African malaria vector Anopheles funestus.Metabolic resistance to pyrethroids driven by cytochrome P450s is threatening malaria control interventions and may provide cross-resistance to insecticides with unrelated modes of action. Here, we show that cytochrome P450 genes CYP6P9a/b associated with pyrethroid resistance in Anopheles funestus also confer cross-resistance to a novel mitochondrial complex I inhibitor insecticide, code-named Sherlock. Using standard bioassays (CDC bottle bioassays, WHO cone bioassays, and WHO tunnel tests), the Sherlock and pyrethroid insecticides were tested against pyrethroid-resistant An. gambiae s.s. (Nkolondom, Cameroon) and An. funestus s.s. (Mibellon, Cameroon) and FUMOZ-R). Molecular assays (genotyping of P450 markers and qRT-PCR expression) were performed to investigate the underlying resistanc2025-01-01T00:00:00Z2025 Sep2026-06-03T21:45:37.455Z2026-05-02T03:08:39.316ZS-EPMC124652884101319510.1186/s12864-025-11984-1