Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus

Leon M J Mugenzi, Benjamin D Menze, Magellan Tchouakui, Murielle J Wondji, Helen Irving, Micareme Tchoupo, Jack Hearn, Gareth D Weedall, Jacob M Riveron, Charles S Wondji

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa. Applying this assay we demonstrate, using semi-field experimental huts, that CYP6P9b-mediated resistance associates with reduced effectiveness of LLINs. Furthermore, we establish that CYP6P9b combines with another P450, CYP6P9a, to additively exacerbate the reduced efficacy of insecticide-treated nets. Double homozygote resistant mosquitoes (RR/RR) significantly survive exposure to insecticide-treated nets and successfully blood feed more than other genotypes. This study provides tools to track and assess the impact of multi-gene driven metabolic resistance to pyrethroids, helping improve resistance management.

Original languageEnglish
Article number4652
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPrint publication - 11 Oct 2019
Externally publishedYes

Keywords

  • Africa
  • Animals
  • Anopheles/drug effects
  • Cytochrome P-450 Enzyme System/genetics
  • Gene Expression Profiling
  • Genotype
  • Insect Proteins/genetics
  • Insecticide Resistance/genetics
  • Insecticide-Treated Bednets
  • Mosquito Control
  • Mosquito Vectors/drug effects
  • Polymorphism, Genetic
  • Pyrethrins/pharmacology

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