Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector

• DOI: 10.1371/journal.pgen.1005618
• Publication Date: 2015-10-30T18:26:47Z
• Authors: Sulaiman S. Ibrahim; Jacob M. Riveron; Jaclyn Bibby; Helen Irving; Cristina Yunta; Mark J. I. Paine; Charles S. Wondji
• Keywords: Anopheles gambiae

Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance pyrethroid insecticides in vectors threatens its continued effectiveness. Deciphering the detailed molecular basis such and designing diagnostic tools is critical implement suitable management strategies. Here, we demonstrated that allelic variation two cytochrome P450 genes most important driver major African vector Anopheles funestus detected key mutations controlling this resistance. An Africa-wide polymorphism analysis duplicated CYP6P9a CYP6P9b revealed both are directionally selected with alleles segregating according phenotypes. Modelling docking simulations predicted resistant were better metabolizers pyrethroids than susceptible alleles. Metabolism assays performed recombinant enzymes various confirmed from mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression Drosophila showed flies expressing more compared those alleles, indicating mechanism. Furthermore, site-directed mutagenesis functional analyses three amino acid changes (Val109Ile, Asp335Glu Asn384Ser) allele inducing high metabolic efficiency. The detection these first DNA markers allows design DNA-based detect track associated bednets scale up, which will improve evidence-based