Evidence map›Paper›PMID 39696366›Full record

ArticleBMC biology2024

Two highly selected mutations in the tandemly duplicated CYP6P4a and CYP6P4b genes drive pyrethroid resistance in Anopheles funestus in West Africa.

Nelly M T Tatchou-Nebangwa, Leon M J Mugenzi, Abdullahi Muhammad, Derrick N Nebangwa, Mersimine F M Kouamo, Carlos S Djoko Tagne, Theofelix A Tekoh, Magellan Tchouakui, Stephen M Ghogomu, Sulaiman S Ibrahim and 1 more

Abstract read
In one paragraph

Article in BMC biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Population genomics ofScience (New York, N.Y.) · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Nelly M T Tatchou-NebangwaCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon. manuela.tchatchoua@crid-cam.net.
Leon M J MugenziCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon.
Abdullahi MuhammadVector Biology Department, Liverpool School of Tropical Medicine (LSTM), Pembroke Place, Liverpool, L3 5QA, UK.
Derrick N NebangwaRandall Center for Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Mersimine F M KouamoCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon.
Carlos S Djoko TagneCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon.
Theofelix A TekohCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon.
Magellan TchouakuiCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon.
Stephen M GhogomuDepartment of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon.
Sulaiman S IbrahimCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon.
Charles S WondjiCentre for Research in Infectious Diseases (CRID), P.O. BOX 13591, Yaounde, Cameroon. charles.wondji@lstmed.ac.uk.

Funding

Bill and Melinda Gates Foundation INV0006003Wellcome Trust 217188/Z/19/Z
6 · The paper itself

Abstract

backgroundGaining 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.

resultsContinent-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.

conclusionsOverall, 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.

Indexed as

AnophelesInsecticide ResistanceInsecticidesMutationPyrethrinsAfrica, WesternAnimalsInsect ProteinsMosquito VectorsInsecticidesInsect ProteinsPyrethrinsAnopheles funestusCytochrome P450GAL4/UAS expressionHeterologous expressionInsecticide metabolism assayInsecticide resistance

Identifiers

PMID39696366
PMCPMC11657943

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.