title: A core metabolic enzyme mediates resistance to phosphine gas.
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.
authors.affiliation: Agri-Science Queensland, Department of Agriculture, Fisheries and Forestry, Ecosciences Precinct, Brisbane, QLD 4001, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Schlipalius
authors.forename: Nicholas
authors.initials: N
authors.lastname: Valmas
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Tuck
authors.forename: Rajeswaran
authors.initials: R
authors.lastname: Jagadeesan
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Kaur
authors.forename: Anita
authors.initials: A
authors.lastname: Goldinger
authors.forename: Cameron
authors.initials: C
authors.lastname: Anderson
authors.forename: Jujiao
authors.initials: J
authors.lastname: Kuang
authors.forename: Steven
authors.initials: S
authors.lastname: Zuryn
authors.forename: Yosep S
authors.initials: YS
authors.lastname: Mau
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Collins
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Nayak
authors.forename: Horst Joachim
authors.initials: HJ
authors.lastname: Schirra
authors.forename: Massimo A
authors.initials: MA
authors.lastname: Hilliard
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ebert
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D001517:Coleoptera / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008058:Dihydrolipoamide Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology; D053858:Metabolic Networks and Pathways; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D010575:Pesticides; D010720:Phosphines / Q000494:pharmacology; D011110:Polymorphism, Genetic; D055503:Protein Multimerization; D014231:Tribolium / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D001152:Arsenicals; D018053:Arsenites; D029742:Caenorhabditis elegans Proteins; D019476:Insect Proteins; D007306:Insecticides; D010575:Pesticides; D010720:Phosphines; D008058:Dihydrolipoamide Dehydrogenase; C044646:phosphine; C015001:arsenite; C006633:arsine