Evidence map›Paper›PMID 34228718›Full record

ArticlePLoS genetics2021

CRISPR/Cas9 modified An. gambiae carrying kdr mutation L1014F functionally validate its contribution in insecticide resistance and combined effect with metabolic enzymes.

Linda Grigoraki, Ruth Cowlishaw, Tony Nolan, Martin Donnelly, Gareth Lycett, Hilary Ranson

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 47 citations in OpenAlex.

  1. 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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  11. An atlas of positive selection in the genomes of major malaria vectors.bioRxiv : the preprint server for biology · 2025
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  19. Discovery of knock-down resistance in the major African malaria vectorbioRxiv : the preprint server for biology · 2024
    Article
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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

6 authors at 1 institution in 1 country.

Linda GrigorakiVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.ORCID 0000-0001-8997-0406
Ruth CowlishawVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.ORCID 0000-0003-2673-5104
Tony NolanVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.ORCID 0000-0002-2982-8333
Martin DonnellyVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.ORCID 0000-0001-5218-1497
Gareth LycettVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.ORCID 0000-0002-2422-053X
Hilary RansonVector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.ORCID 0000-0003-2332-8247
Liverpool School of Tropical Medicine · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F021933/1Medical Research Council MR/V001264/1Wellcome TrustWellcome Trust 215894/Z/19/Z
6 · The paper itself

Abstract

Insecticide resistance in Anopheles mosquitoes is a major obstacle in maintaining the momentum in reducing the malaria burden; mitigating strategies require improved understanding of the underlying mechanisms. Mutations in the target site of insecticides (the voltage gated sodium channel for the most widely used pyrethroid class) and over-expression of detoxification enzymes are commonly reported, but their relative contribution to phenotypic resistance remain poorly understood. Here we present a genome editing pipeline to introduce single nucleotide polymorphisms in An. gambiae which we have used to study the effect of the classical kdr mutation L1014F (L995F based on An. gambiae numbering), one of the most widely distributed resistance alleles. Introduction of 1014F in an otherwise fully susceptible genetic background increased levels of resistance to all tested pyrethroids and DDT ranging from 9.9-fold for permethrin to >24-fold for DDT. The introduction of the 1014F allele was sufficient to reduce mortality of mosquitoes after exposure to deltamethrin treated bednets, even as the only resistance mechanism present. When 1014F was combined with over-expression of glutathione transferase Gste2, resistance to permethrin increased further demonstrating the critical combined effect between target site resistance and detoxification enzymes in vivo. We also show that mosquitoes carrying the 1014F allele in homozygosity showed fitness disadvantages including increased mortality at the larval stage and a reduction in fecundity and adult longevity, which can have consequences for the strength of selection that will apply to this allele in the field.

Indexed as

CRISPR-Cas SystemsMutationAnimalsAnimals, Genetically ModifiedAnophelesDDTFemaleFertilityGenome, InsectGlutathione TransferaseInsecticide ResistanceInsect ProteinsMaleNitrilesPermethrinPiperonyl ButoxideDDTdecamethrinGlutathione TransferaseInsect ProteinsNitrilesPermethrinPiperonyl ButoxidePyrethrins

Identifiers

PMID34228718
PMCPMC8284791
OpenAlexW3180778936

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.