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Tatchou-Nebangwa, Nelly M. T., Mugenzi, Leon M. J., Muhammad, Abdullahi, Nebangwa, Derrick N., Kouamo, Mersimine F. M., Tagne, Carlos S. Djoko, Tekoh, Theofelix A., Tchouakui, Magellan, Ghogomu, Stephen M., Ibrahim, Sulaiman S. and Wondji, Charles S. 
ORCID: https://orcid.org/0000-0003-0791-3673
(2024)
'Two highly selected mutations in the tandemly duplicated CYP6P4a and CYP6P4b genes drive pyrethroid resistance in Anopheles funestus in West Africa'. BMC biology, Vol 22, Issue 1.
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12915_2024_Article_2081.pdf - Published Version Available under License Creative Commons Attribution. Download (4MB) | Preview |
Abstract
Background
Gaining a comprehensive understanding of the genetic mechanisms underlying insecticide resistance in malaria vectors is crucial for optimising the effectiveness of insecticide-based vector control methods and developing diagnostic tools for resistance management. Considering the heterogeneity of metabolic resistance in major malaria vectors, the implementation of tailored resistance management strategies is essential for successful vector control. Here, we provide evidence demonstrating that two highly selected mutations in CYP6P4a and CYP6P4b are driving pyrethroid insecticide resistance in the major malaria vector Anopheles funestus, in West Africa.
Results
Continent-wide polymorphism survey revealed escalated signatures of directional selection of both genes between 2014 and 2021. In vitro insecticide metabolism assays with recombinant enzymes from both genes showed that mutant alleles under selection exhibit higher metabolic efficiency than their wild-type counterparts. Using the GAL4-UAS expression system, transgenic Drosophila flies overexpressing mutant alleles exhibited increased resistance to pyrethroids. These findings were consistent with in silico predictions which highlighted changes in enzyme active site architecture that enhance the affinity of mutant alleles for type I and II pyrethroids. Furthermore, we designed two DNA-based assays for the detection of CYP6P4a-M220I and CYP6P4b-D284E mutations, showing their current confinement to West Africa. Genotype/phenotype correlation analyses revealed that these markers are strongly associated with resistance to types I and II pyrethroids and combine to drastically reduce killing effects of pyrethroid bed nets.
Conclusions
Overall, this study demonstrated that CYP6P4a and CYP6P4b contribute to pyrethroid resistance in An. funestus and provided two additional insecticide resistance molecular diagnostic tools that would contribute to monitoring and better management of resistance.
| Item Type: | Article |
|---|---|
| Subjects: | QX Parasitology > Insects. Other Parasites > QX 515 Anopheles WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria |
| Faculty: Department: | Biological Sciences > Vector Biology Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1186/s12915-024-02081-y |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 14 Jan 2025 08:46 |
| Last Modified: | 14 Jan 2025 08:46 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25864 |
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