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

Mugenzi, LMJ, Menze, BD, Tchouakui, M, Wondji, MJ, Irving, H, Tchoupo, M, Hearn, J, Weedall, GD, Riveron, JM and Wondji, CS (2019) Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus. Nature Communications, 10. ISSN 2041-1723

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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.

Item Type: Article
Uncontrolled Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; PYRETHROID RESISTANCE; GAMBIAE; GENE; OVEREXPRESSION; IDENTIFICATION; MECHANISMS; TOOL
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RM Therapeutics. Pharmacology
Divisions: Biological & Environmental Sciences (new Sep 19)
Publisher: Nature Publishing Group
Related URLs:
Date Deposited: 14 Nov 2019 09:11
Last Modified: 14 Nov 2019 09:15
DOI or Identification number: 10.1038/s41467-019-12686-5
URI: http://researchonline.ljmu.ac.uk/id/eprint/11765

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