N318L Blocks the Interaction of Fluralaner but Not Broflanilide or Fipronil with the Insect GABA Receptor In Vivo

文献类型： 外文期刊

第一作者： Zhang, Yichi

作者： Zhang, Yichi;Liu, Xinyu;Wang, Junyan;Wang, Ying;Amponsah, Priscilla;Zhao, Chunqing;Tang, Tao;Jones, Andrew K.

作者机构：

关键词： chloride channel; resistanceto dieldrin; isoxazolines; Drosophila; CRISPR/Cas9

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：6.2； 五年影响因子：6.4 ）

ISSN： 0021-8561

年卷期： 2024 年 72 卷 41 期

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收录情况： SCI

摘要： Fluralaner is a novel insecticide targeting the ionotropic GABA receptor (GABAR) subunit, RDL. A recent study revealed that N316L, a substitution of asparagine (N) with leucine (L), in the second transmembrane (M2)-spanning region reduced the antagonist action of fluralaner on the housefly Musca domestica RDL (MdRDL) in vitro. To verify the impact of N316L in vivo, the corresponding mutation (N318L) in the fruitfly Drosophila melanogaster RDL (DmRDL) was constructed using CRISPR/Cas9 genome editing. The homozygous DmRDL(N318L) mutant showed a 9.87-fold resistance to fluralaner compared with w(1118) while still being highly sensitive to broflanilide and fipronil, which is consistent with those findings observed in the electrophysiology assays of the homomeric DmRDL(WT) or DmRDL(N318L) channel. Moreover, DmRDL(N318L) led to malformed ovaries, stunted eggs, and sterility in homozygous females. These results highlighted N318 as a molecular site for fluralaner in vivo and in vitro and might elucidate the resistance mechanisms of insects against fluralaner.

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