期刊
SCIENCE ADVANCES
卷 8, 期 47, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abq3132
关键词
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资金
- Natural Science Foundation of Zhejiang Province [LR19C140002]
- National Natural Science Foundation of China [31802019, 32072496]
- National Institute of Allergy and Infectious Diseases [AI165575]
- National Institute on Deafness and Other Communication Disorders [DC007864]
This study identified nicotinamidase (Naam) as a previously unknown molecular target for the insecticide flonicamid. Inhibition of Naam by a metabolite of flonicamid led to defects in gravity sensing in flies. The resistance of bees to flonicamid was due to a gene duplication.
Hundreds of neurotoxic insecticides are currently in use. However, only a few direct targets have been identified. Here, using Drosophila and the insecticide flonicamid, we identified nicotinamidase (Naam) as a previous unidentified molecular target for an insecticide. Naam is expressed in chordotonal stretch-receptor neurons, and inhibition of Naam by a metabolite of flonicamid, TFNA-AM (4-trifluoromethylnicotinamide), induces accumulation of substrate nico-tinamide and greatly inhibits negative geotaxis. Engineered flies harboring a point mutation in the active site show insecticide resistance and defects in gravity sensing. Bees are resistant to flonicamid because of a gene duplication, resulting in the generation of a TFNA-AM-insensitive Naam. Our results, in combination with the absence of genes encoding Naam in vertebrate genomes, suggest that TFNA-AM and potential species-specific Naam inhibitors could be developed as novel insecticides, anthelmintics, and antimicrobials for agriculture and human health.
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