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

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

Research output: Contribution to journal › Article › peer-review

86 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	Published - 11 Oct 2019

UN SDGs

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

Access to Document

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

NCOMMS-19-03372B 2 Accepted 240919Accepted author manuscript, 150 KBLicence: CC BY

Impact of glutathione-s transferase and cytochrome P450 metabolic resistance on the effectiveness of various bed nets against Anopheles funestus, a major malaria vector in Africa
Menze, B. (Author), Wondji, C. (Supervisor), 2020
Student thesis: Doctoral thesis

File

Cite this

@article{3557f59aa030412c9a8802c2d1c99af9,

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.",

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

year = "2019",

month = oct,

day = "11",

doi = "10.1038/s41467-019-12686-5",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus

AU - Mugenzi, Leon M.J.

AU - Menze, Benjamin

AU - Tchouakui, Magellan

AU - Wondji, Murielle

AU - Irving, Helen

AU - Tchoupo, Micareme

AU - Hearn, Jack

AU - Weedall, Gareth D.

AU - Riveron, Jacob M.

AU - Wondji, Charles

PY - 2019/10/11

Y1 - 2019/10/11

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.

AB - 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.

U2 - 10.1038/s41467-019-12686-5

DO - 10.1038/s41467-019-12686-5

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4652

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Student theses

Impact of glutathione-s transferase and cytochrome P450 metabolic resistance on the effectiveness of various bed nets against Anopheles funestus, a major malaria vector in Africa

Cite this