A core metabolic enzyme mediates resistance to phosphine gas.
basic_science · Level V
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- Record sourced from PubMed, PMID 23139334.
- Also identified by DOI 10.1126/science.1224951.
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Abstract
Phosphine is a small redox-active gas that is used to protect global grain reserves, which are threatened by the emergence of phosphine resistance in pest insects. We find that polymorphisms responsible for genetic resistance cluster around the redox-active catalytic disulfide or the dimerization interface of dihydrolipoamide dehydrogenase (DLD) in insects (Rhyzopertha dominica and Tribolium castaneum) and nematodes (Caenorhabditis elegans). DLD is a core metabolic enzyme representing a new class of resistance factor for a redox-active metabolic toxin. It participates in four key steps of core metabolism, and metabolite profiles indicate that phosphine exposure in mutant and wild-type animals affects these steps differently. Mutation of DLD in C. elegans increases arsenite sensitivity. This specific vulnerability may be exploited to control phosphine-resistant insects and safeguard food security.
Medical subject headings
- Animals
- Arsenicals
- Arsenicals/pharmacology
- Arsenites
- Arsenites/pharmacology
- Caenorhabditis elegans
- Caenorhabditis elegans/drug effects
- Caenorhabditis elegans/enzymology
- Caenorhabditis elegans/genetics
- Caenorhabditis elegans/metabolism
- Caenorhabditis elegans Proteins
- Caenorhabditis elegans Proteins/chemistry
- Caenorhabditis elegans Proteins/genetics
- Caenorhabditis elegans Proteins/metabolism
- Catalytic Domain
- Coleoptera
- Coleoptera/drug effects
- Coleoptera/enzymology
- Coleoptera/genetics
- Coleoptera/metabolism
- Dihydrolipoamide Dehydrogenase
- Dihydrolipoamide Dehydrogenase/chemistry
- Dihydrolipoamide Dehydrogenase/genetics
- Dihydrolipoamide Dehydrogenase/metabolism
- Insect Proteins
- Insect Proteins/chemistry
- Insect Proteins/genetics
- Insect Proteins/metabolism
- Insecticide Resistance
- Insecticide Resistance/genetics
- Insecticides
- Insecticides/pharmacology
- Metabolic Networks and Pathways
- Molecular Sequence Data
- Mutation
- Oxidation-Reduction
- Pesticides
- Phosphines
- Phosphines/pharmacology
- Polymorphism, Genetic
- Protein Multimerization
- Tribolium
- Tribolium/drug effects
- Tribolium/enzymology
- Tribolium/genetics
- Tribolium/metabolism