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.

Details

Title
Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus
Author
Mugenzi, Leon M J 1 ; Menze, Benjamin D 2 ; Magellan Tchouakui 3 ; Wondji, Murielle J 2 ; Irving, Helen 4 ; Tchoupo, Micareme 3 ; Hearn, Jack 4   VIAFID ORCID Logo  ; Weedall, Gareth D 5 ; Riveron, Jacob M 2 ; Wondji, Charles S 2   VIAFID ORCID Logo 

1  Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, UK; Centre for Research in Infectious Diseases (CRID), Yaoundé, Cameroon; Department of Biochemistry and Molecular Biology, Faculty of Science University of Buea, Buea, Cameroon 
2  Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, UK; Centre for Research in Infectious Diseases (CRID), Yaoundé, Cameroon 
3  Centre for Research in Infectious Diseases (CRID), Yaoundé, Cameroon 
4  Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, UK 
5  Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, UK; School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool, UK 
Pages
1-11
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-12686-5
ProQuest document ID
2304108095
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.