Journal Article


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

Abstract

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 DmRDLN318L mutant showed a 9.87-fold resistance to fluralaner compared with w1118 while still being highly sensitive to broflanilide and fipronil, which is consistent with those findings observed in the electrophysiology assays of the homomeric DmRDLWT or DmRDLN318L channel. Moreover, DmRDLN318L 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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Authors

Zhang Yichi
Liu Xinyu
Wang Junyan
Wang Ying
Amponsah, Priscilla
Tang Tao
Jones, Andrew J.
Zhao Chunqing

Oxford Brookes departments

School of Biological and Medical Sciences

Dates

Year of publication: 2024
Date of RADAR deposit: 2024-10-08



“This document is the unedited author’s version of a work accepted for publication in Journal of Agricultural and Food Chemistry, copyright © 2024 after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.jafc.4c06478."


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