• DOI:10.1126/science.1224951
• Corpus ID: 10390339

A Core Metabolic Enzyme Mediates Resistance to Phosphine Gas

@article{Schlipalius2012ACM,
  title={A Core Metabolic Enzyme Mediates Resistance to Phosphine Gas},
  author={David I Schlipalius and Nicholas Valmas and Andrew G. Tuck and Rajeswaran Jagadeesan and Li Ma and Ramandeep Kaur and Anita Goldinger and Cameron Anderson and Jujiao Kuang and Steven Zuryn and Yosep Seran Mau and Qiang Cheng and Patrick J. Collins and Manoj Kumar Nayak and Horst Joachim Schirra and Massimo A. Hilliard and Paul R Ebert},
  journal={Science},
  year={2012},
  volume={338},
  pages={807 - 810}
}

• D. Schlipalius, Nicholas Valmas, +14 authors P. Ebert
• Published 9 November 2012
• Biology, Medicine
• Science

Dissecting Phosphine Resistance Worldwide populations of pest insects—such as the lesser grain borer, Rhyzopertha dominica, and the rust-red flour beetle, Tribolium castaneum—have become highly resistant to the fumigant phosphine, providing a potential threat to global food security. The nematode, Caenorhabditis elegans is vulnerable to phosphine, but phosphine-resistant strains are known. Schlipalius et al. (p. 807) show that mutations in the delta-1-pyrroline-5-carboxylate dehydrogenase and dihydrolipoamide dehydrogenase (dld-1) genes both give rise to phosphine resistance in C. elegans. Phosphine resistance mutants in R. dominica, and T. castaneum also map to the dld-1 gene, which codes for a core metabolic enzyme. These mutants are, however, hypersensitive to arsenic, mimics of which might thus synergize with phosphine. Mutations in a lipoic acid metabolism enzyme confer resistance to phosphine but also result in sensitivity to arsenite. 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.