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

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Scale up of Long Lasting Insecticide Nets has massively reduced malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Here, we established that allelic variation in two CYP450s is the most important driver of pyrethroid resistance in the major African vector Anopheles funestus and detected key mutations controlling this resistance. The duplicated P450s CYP6P9a and CYP6P9b are directionally selected across Africa with alleles segregating according to resistance phenotypes. Alleles from resistant mosquitoes present significantly higher metabolic activities toward pyrethroids compared with alleles from susceptible mosquitoes. Furthermore, transgenic flies over-expressing resistant alleles of both genes were significantly more resistant to pyrethroids. Three amino acid changes from the resistant CYP6P9b allele are the key pyrethroid resistance mutations which induce high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of diagnostic tools to detect and track resistance.

Vyšlo v časopise: Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005618
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005618

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