Exploiting muscarinic acetylcholine receptors as an insecticidal target to enhance the toxicity of gamma-amino butyric acid channel blockers and the continued challenges with resistance

Muscarinic acetylcholine receptors (mAChRs) are G-protein-coupled receptors that are underutilized for controlling insect pests despite their involvement in various physiological functions. To-date, there are no commercialized insecticides targeting insect mAChRs. In this dissertation, effective target-site synergism was demonstrated in susceptible Drosophila melanogaster where mAChR agonism by pilocarpine enhanced the toxicity of insecticides targeting gamma-aminobutyric acid (GABA)-gated chloride channels, indicating the potential of insect mAChRs as a target for developing novel insecticides/synergists to control resistant pests. A point mutation (A301S) in the GABA-gated chloride channel confers resistance to dieldrin (Rdl), lindane, and fipronil, which I have confirmed using different routes of exposure. However, the same synergistic effect was not achieved in the resistant strain with the presence of this target-site mutation. This difference between two strains is perplexing because there is a change in the efficacy of several compound classes that do not directly act upon GABA-gated chloride channels. Specifically, a point mutation appears to influence how the insect central nervous system (CNS) responds to muscarinic compounds, type I pyrethroids, and acetylcholinesterase (AChE) inhibitors. In the case of acetylcholinesterase, the resistant insect increases the expression of Ace gene encoding this enzyme. Fully understanding how the CNS responds to receptor modifications is not well understood and could have a significant impact to pest management strategies.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Entomology

Department dc:contributor.department

Entomology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2022

Author dc:creator

• Xie, Na

Chair dc:contributor.committeechair

• Gross, Aaron Donald

Committee members dc:contributor.committeemember

• Carlier, Paul R.
• Vinauger, Clément
• Kuhar, Thomas P.
• Bloomquist, Jeffrey R.

• Target-site Synergism
• Acetylcholinesterase (AChE)
• Rdl mutation
• Drosophila melanogaster

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:34508

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/110120