Journal Article

A core metabolic enzyme mediates resistance to phosphine gas

Valmas, N, Tuck, Andrew G, Kaur, Ramandeep, Anderson, C, Nayak, Manoj K, Hilliard, M. A, Cheng, Q, Goldinger, A, Maddock, L, Mau, Y.S, Kuang, J, Collins, Patrick J, Zuryn, S, Jagadeesan, Rajeswaran, Ebert, P. R, Schlipalius, David I, Schirra, H. J

2012

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Alleles / Animals / Arsenic / Arsenicals - pharmacology / Arsenites - pharmacology / Beetles / Biological and medical sciences / Caenorhabditis elegans / Caenorhabditis elegans - drug effects / Caenorhabditis elegans - enzymology / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - chemistry / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Catalytic Domain / Coleoptera - drug effects / Coleoptera - enzymology / Coleoptera - genetics / Coleoptera - metabolism / Dehydrogenase / Dihydrolipoamide Dehydrogenase - chemistry / Dihydrolipoamide Dehydrogenase - genetics / Dihydrolipoamide Dehydrogenase - metabolism / Disulfides / Dominica / Enzymes / Flour / Food security / Food supply / Foods / fumigants / Fundamental and applied biological sciences. Psychology / Genes / Genetic mutation / Insect genetics / Insect pests / Insect Proteins - chemistry / Insect Proteins - genetics / Insect Proteins - metabolism / Insecticide Resistance - genetics / Insecticides - pharmacology / Insects / Invertebrates / Medically important nuisances and vectors, pests of stored products and materials: population survey and control / Metabolic Networks and Pathways / Metabolism / Metabolites / Molecular Sequence Data / Mutagenesis / mutants / Mutation / Nematoda / Nematodes / Oxidation-Reduction / Pest control / Pesticides / Pests / Pests of stored products / phosphine / Phosphines / Phosphines - pharmacology / Polymorphism, Genetic / Protein Multimerization / Resistance to control / Rhyzopertha dominica / Toxins / Tribolium - drug effects / Tribolium - enzymology / Tribolium - genetics / Tribolium - metabolism / Tribolium castaneum