Evidence map›Paper›PMID 24675797›Full record

ArticlePloS one2014

Metabolic and target-site mechanisms combine to confer strong DDT resistance in Anopheles gambiae.

Sara N Mitchell, Daniel J Rigden, Andrew J Dowd, Fang Lu, Craig S Wilding, David Weetman, Samuel Dadzie, Adam M Jenkins, Kimberly Regna, Pelagie Boko and 6 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
8.7field-weighted citation impact, top 2% of its field
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

88 citing papers in PubMed, 155 citations in OpenAlex.

  1. Trial
  2. Synergistic action of different molecular mechanisms causes striking levels of insecticide resistance in the malaria vectorProceedings of the National Academy of Sciences of the United States of America · 2026
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  8. Distinct Genetic Footprint of Adaptation Observed WithinResearch and reports in tropical medicine · 2026
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  13. Evaluation of the efficacy of 20% IR3535Parasites & vectors · 2025
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  15. An atlas of positive selection in the genomes of major malaria vectors.bioRxiv : the preprint server for biology · 2025
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  20. Science advances · 2024
    Article

28 more citing papers are in PubMed but not listed here.

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

16 authors at 6 institutions in 4 countries.

Sara N MitchellDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Daniel J RigdenInstitute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Andrew J DowdDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Fang LuInstitute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Craig S WildingDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
David WeetmanDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Samuel DadzieDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
Adam M JenkinsBoston College, Chestnut Hill, Massachusetts, United States of America.
Kimberly RegnaBoston College, Chestnut Hill, Massachusetts, United States of America.
Pelagie BokoDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Luc DjogbenouInstitut Régional de Santé Publique de Ouidah/Université d'Abomey-Calavi, Cotonou, Bénin.
Marc A T MuskavitchBoston College, Chestnut Hill, Massachusetts, United States of America; Harvard School of Public Health, Boston, Massachusetts, United States of America.
Hilary RansonDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Mark J I PaineDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Olga MayansInstitute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Martin J DonnellyDepartment of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
Liverpool School of Tropical Medicine · GBBoston College · USUniversity of Liverpool · GBUniversité d'Abomey-Calavi · BJUniversity of Ghana · GHWellcome Sanger Institute · GB

Funding

Development of a Field Applicable Screening Tool (FAST) kit for detecting resistaR01AI082734 · NIAID · TMLIVERPOOL SCHOOL OF TROPICAL MEDICINE · PI DONNELLY, MARTIN JAMES · 2009 to 2013
$1.6M
Biotechnology and Biological Sciences Research CouncilNIAID NIH HHS R01 AI082734NIAID NIH HHS R01AI082734
6 · The paper itself

Abstract

The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae.

Indexed as

AfricaAllelesAmino Acid SubstitutionAnimalsAnophelesCatalysisDDTEnzyme ActivationFemaleGene ExpressionGenes, InsectGenetic VariationHaplotypesInsecticide ResistanceInsecticidesModels, MolecularDDTInsecticidesRecombinant Proteins

Identifiers

PMID24675797
PMCPMC3968025
OpenAlexW2163804597

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.