Cargando…

An insecticide target in mechanoreceptor neurons

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 chordoton...

Descripción completa

Detalles Bibliográficos
Autores principales: Qiao, Xiaomu, Zhang, Xiaoyu, Zhou, Zhendong, Guo, Lei, Wu, Weiping, Ma, Suhan, Zhang, Xinzhong, Montell, Craig, Huang, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683716/
https://www.ncbi.nlm.nih.gov/pubmed/36417522
http://dx.doi.org/10.1126/sciadv.abq3132
_version_ 1784835114835902464
author Qiao, Xiaomu
Zhang, Xiaoyu
Zhou, Zhendong
Guo, Lei
Wu, Weiping
Ma, Suhan
Zhang, Xinzhong
Montell, Craig
Huang, Jia
author_facet Qiao, Xiaomu
Zhang, Xiaoyu
Zhou, Zhendong
Guo, Lei
Wu, Weiping
Ma, Suhan
Zhang, Xinzhong
Montell, Craig
Huang, Jia
author_sort Qiao, Xiaomu
collection PubMed
description 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 nicotinamide 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.
format Online
Article
Text
id pubmed-9683716
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Association for the Advancement of Science
record_format MEDLINE/PubMed
spelling pubmed-96837162022-12-05 An insecticide target in mechanoreceptor neurons Qiao, Xiaomu Zhang, Xiaoyu Zhou, Zhendong Guo, Lei Wu, Weiping Ma, Suhan Zhang, Xinzhong Montell, Craig Huang, Jia Sci Adv Neuroscience 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 nicotinamide 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. American Association for the Advancement of Science 2022-11-23 /pmc/articles/PMC9683716/ /pubmed/36417522 http://dx.doi.org/10.1126/sciadv.abq3132 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Neuroscience
Qiao, Xiaomu
Zhang, Xiaoyu
Zhou, Zhendong
Guo, Lei
Wu, Weiping
Ma, Suhan
Zhang, Xinzhong
Montell, Craig
Huang, Jia
An insecticide target in mechanoreceptor neurons
title An insecticide target in mechanoreceptor neurons
title_full An insecticide target in mechanoreceptor neurons
title_fullStr An insecticide target in mechanoreceptor neurons
title_full_unstemmed An insecticide target in mechanoreceptor neurons
title_short An insecticide target in mechanoreceptor neurons
title_sort insecticide target in mechanoreceptor neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683716/
https://www.ncbi.nlm.nih.gov/pubmed/36417522
http://dx.doi.org/10.1126/sciadv.abq3132
work_keys_str_mv AT qiaoxiaomu aninsecticidetargetinmechanoreceptorneurons
AT zhangxiaoyu aninsecticidetargetinmechanoreceptorneurons
AT zhouzhendong aninsecticidetargetinmechanoreceptorneurons
AT guolei aninsecticidetargetinmechanoreceptorneurons
AT wuweiping aninsecticidetargetinmechanoreceptorneurons
AT masuhan aninsecticidetargetinmechanoreceptorneurons
AT zhangxinzhong aninsecticidetargetinmechanoreceptorneurons
AT montellcraig aninsecticidetargetinmechanoreceptorneurons
AT huangjia aninsecticidetargetinmechanoreceptorneurons
AT qiaoxiaomu insecticidetargetinmechanoreceptorneurons
AT zhangxiaoyu insecticidetargetinmechanoreceptorneurons
AT zhouzhendong insecticidetargetinmechanoreceptorneurons
AT guolei insecticidetargetinmechanoreceptorneurons
AT wuweiping insecticidetargetinmechanoreceptorneurons
AT masuhan insecticidetargetinmechanoreceptorneurons
AT zhangxinzhong insecticidetargetinmechanoreceptorneurons
AT montellcraig insecticidetargetinmechanoreceptorneurons
AT huangjia insecticidetargetinmechanoreceptorneurons