What question did this study set out to answer?

To elucidate the molecular, structural, and genetic mechanisms underlying high-level DDT resistance in the African malaria vector Anopheles gambiae.

March 27, 2014PLoS ONEOpen Access

Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

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To elucidate the molecular, structural, and genetic mechanisms underlying high-level DDT resistance in the African malaria vector Anopheles gambiae.
Sequenced the Gste2 detoxification gene in DDT-resistant and susceptible Anopheles gambiae strains and analyzed recombinant enzyme kinetics.
Determined the crystal structure of the GSTE2 I114T mutant using X-ray crystallography and evaluated DDT tolerance via transgenic expression in Drosophila melanogaster.
Genotyped wild-caught M-form Anopheles gambiae populations to evaluate associations between the Gste2-114T mutation, target-site Vgsc mutations (1014F and 1575Y), and DDT resistance.
Identified a non-synonymous I114T mutation in GSTE2 that prevents substrate inhibition at high DDT concentrations and confers DDT tolerance when expressed in Drosophila.
X-ray crystallography revealed that the I114T substitution places a hydroxyl group near the hydrophobic DDT-binding site to enhance local enzyme dynamics without altering the overall protein fold.
The Gste2-114T mutation acts synergistically with voltage-gated sodium channel mutations (Vgsc-1575Y and Vgsc-1014F) to produce extreme DDT resistance in wild populations.

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Implication

Laboratory and genetic study reveals combined Gste2 and Vgsc mutations confer extreme DDT resistance in Anopheles gambiae, highlighting multi-mechanism insecticide resistance evolution.

Cite This Study

Mitchell et al. (2014) studied this question.

synapsesocial.com/papers/69d8777fe9c100a435ae2b78 https://doi.org/10.1371/journal.pone.0092662

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Implication

Laboratory and genetic study reveals combined Gste2 and Vgsc mutations confer extreme DDT resistance in Anopheles gambiae, highlighting multi-mechanism insecticide resistance evolution.

Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

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Discussion

Implication

Cite This Study

Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

Key Points

Discussion

Implication

Cite This Study

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