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 and Charles S. Wondji ()
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Leon M. J. Mugenzi: Liverpool School of Tropical Medicine
Benjamin D. Menze: Liverpool School of Tropical Medicine
Magellan Tchouakui: Centre for Research in Infectious Diseases (CRID)
Murielle J. Wondji: Liverpool School of Tropical Medicine
Helen Irving: Liverpool School of Tropical Medicine
Micareme Tchoupo: Centre for Research in Infectious Diseases (CRID)
Jack Hearn: Liverpool School of Tropical Medicine
Gareth D. Weedall: Liverpool School of Tropical Medicine
Jacob M. Riveron: Liverpool School of Tropical Medicine
Charles S. Wondji: Liverpool School of Tropical Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12686-5

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