An insecticide target in mechanoreceptor neurons

Area of Science:

• Entomology
• Neuroscience
• Toxicology

Background:

• Numerous neurotoxic insecticides exist, yet their specific molecular targets remain largely unknown.
• Understanding insecticide targets is crucial for developing safer and more effective pest control strategies.

Purpose of the Study:

• To identify the molecular target of the insecticide flonicamid in *Drosophila*.
• To investigate the role of this target in insect physiology and insecticide resistance.

Main Methods:

• Utilized *Drosophila* melanogaster as a model organism.
• Employed genetic engineering to create flies with mutated nicotinamidase (Naam).
• Analyzed the effects of flonicamid metabolite TFNA-AM on Naam activity and insect behavior.

Main Results:

• Identified nicotinamidase (Naam) as the molecular target of flonicamid.
• Flonicamid's metabolite, TFNA-AM, inhibits Naam, leading to nicotinamide accumulation and impaired negative geotaxis in flies.
• Engineered flies with mutated Naam exhibited resistance to flonicamid and defects in gravity sensing.
• Bees possess a TFNA-AM-insensitive Naam due to gene duplication, conferring resistance to flonicamid.

Conclusions:

• Nicotinamidase (Naam) is a previously unrecognized molecular target for insecticides like flonicamid.
• TFNA-AM and species-specific Naam inhibitors show potential as novel insecticides, anthelmintics, and antimicrobials.
• The absence of Naam genes in vertebrates suggests a favorable safety profile for potential therapeutic applications.