ArticleBMC genomics2025
The duplicated cytochrome P450 CYP6P9a/b confers cross-resistance to a mitochondrial complex I inhibitor in the African malaria vector Anopheles funestus.
Article in BMC genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Association between persistent organic pollutants and malaria incidence in mainland China: a population-based surveillance and modeling analysis.BMC public health · 2026Article
- Genomic signatures of selection inbioRxiv : the preprint server for biology · 2026Article
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8 authors.
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Abstract
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 resistance mechanisms and cross-resistance in An. funestus. Field sampled strains of An. gambiae s.s. and An. funestus s.s. from Cameroon were fully susceptible to Sherlock, whereas moderate resistance was observed in the FUMOZ-R An. funestus strain. Genotypic analysis of hybrid mosquitoes demonstrated a correlation between pyrethroid-resistance markers and reduced susceptibility to Sherlock. Individuals carrying one CYP6P9a_R allele had significantly higher odds of surviving exposure to Sherlock compared to those lacking this allele, as evidenced by CDC bottle bioassays (1xDC: OR = 5.3, CI = 2.7-9.8, p < 0.0001; 5xDC: OR = 18.6, CI = 7.8-46.4, p < 0.0001)), cone bioassays (OR = 5.1, CI = 2.7-9.8, p < 0.0001), and tunnel tests (OR = 6.6, CI = 3.4-12.6 p < 0.0001). qRT-PCR analysis revealed elevated expression of CYP6P9a in surviving hybrid mosquitoes exposed to Sherlock and permethrin, as observed in CDC bottle bioassays (1xDC: FC = 24.7; 5xDC: FC = 45.6; permethrin: FC = 35.4) and cone bioassays (FC = 9.8; FC = 4.8, respectively). These findings were consistent with the patterns of CYP6P9b and the 6.5 kb insertion. The L119F_GSTe2 pyrethroid resistance marker did not confer cross-resistance to Sherlock. These findings highlight the importance of considering cross-resistance patterns in the development and deployment of new insecticides for malaria vector control.
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