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

doi:10.1038/s41467-019-12686-5

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 journal › Article › peer-review

72 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 language	English
Article number	4652
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12686-5
Publication status	Print publication - 11 Oct 2019
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-12686-5Licence: CC BY

Cite this

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

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.",

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",

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

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AU - Mugenzi, Leon M J

AU - Menze, Benjamin D

AU - Tchouakui, Magellan

AU - Wondji, Murielle J

AU - Irving, Helen

AU - Tchoupo, Micareme

AU - Hearn, Jack

AU - Weedall, Gareth D

AU - Riveron, Jacob M

AU - Wondji, Charles S

PY - 2019/10/11

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N2 - 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.

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