The P450 CYP6Z1 confers carbamate/pyrethroid cross‐resistance in a major African malaria vector beside a novel carbamate‐insensitive N485I acetylcholinesterase‐1 mutation

• DOI: 10.1111/mec.13673
• Publication Date: 2016-05-02T16:25:30Z
• Authors: Sulaiman S. Ibrahim; Miranda Ndula; Jacob M. Riveron; Helen Irving; Charles S. Wondji
• Keywords: Carbamate; Carboxylesterase

Carbamates are increasingly used for vector control notably in areas with pyrethroid resistance. However, a cross-resistance between these insecticides major malaria vectors such as Anopheles funestus could severely limit available resistance management options. Unfortunately, the molecular basis of remains uncharacterized An. funestus, preventing effective management. Here, using genomewide transcription profiling, we revealed that metabolic through upregulation cytochrome P450 genes is driving carbamate The P450s CYP6P9a, CYP6P9b and CYP6Z1 were most upregulated detoxification multiple resistant mosquitoes. silico docking simulations predicted to metabolize both pyrethroids carbamates, whereas CYP6P9a only pyrethroids. Using recombinant enzyme metabolism inhibition assays, demonstrated metabolizes bendiocarb pyrethroids, Other gene families mosquitoes included several cuticular protein suggesting possible reduced penetration mechanism. Investigation target-site acetylcholinesterase 1 (ace-1) detected established association new N485I mutation (odds ratio 7.3; P < 0.0001). detection haplotypes single after cloning suggested duplication ace-1. A TaqMan genotyping nine countries located southern Africa frequency 10-15% its recent occurrence. These findings will help monitoring spread evolution improve design strategies this vector.