Journal article
Grapefruit-derived nootkatone potentiates GABAergic signaling and acts as a dual-action mosquito repellent and insecticide
Current biology, v 35(1)
25 Nov 2024
PMID: 39631399
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Humanity has long battled mosquitoes and the diseases they transmit-a struggle intensified by climate change and globalization, which have expanded mosquito ranges and the spread of associated diseases.
Additionally, widespread insecticide resistance has reduced the efficacy of current control methods, necessitating new solutions.
Nootkatone, a natural compound found in grapefruit, shows promise as both a mosquito repellent and an insecticide.
However, its mechanism of action remains unclear. Our study demonstrates that nootkatone acts as a potent spatial and contact repellent against multiple mosquito species. Nootkatone-induced spatial aversion, which is influenced by human odor, is in Aedes aegypti partially mediated by Orco- and ionotropic receptor (IR)-positive neurons, while contact aversion is robust and likely mediated via the proboscis and independent of TRPA1 and IRs. We further find that nootkatone potentiates γ-aminobutyric acid (GABA)-mediated signaling by modulating the broadly expressed major insect GABA-gated chloride channel resistant to dieldrin (Rdl). At low doses, the chemosensory-mediated spatial and contact repellency is likely strengthened by nootkatone's disruption of synaptic transmission in select mosquito sensory neurons. At higher doses, nootkatone induces paralysis and death, presumably through broad-range synaptic transmission disruption. These findings reveal nootkatone's unique mode of action and highlight its potential as an effective mosquito control agent. Its dual role as a repellent and an insecticide, combined with low-to-no toxicity to humans and a pleasant smell, underscores nootkatone's promise as a future tool in mosquito control efforts.
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Details
- Title
- Grapefruit-derived nootkatone potentiates GABAergic signaling and acts as a dual-action mosquito repellent and insecticide
- Creators
- Merybeth Fernandez TrianaFelipe AndreazzaNadia MeloRickard IgnellAli AfifyYuan LiDan-Dan ZhangChristopher J PotterKe DongMarcus C Stensmyr
- Publication Details
- Current biology, v 35(1)
- Publisher
- CELL PRESS
- Number of pages
- 17
- Grant note
- Max Planck Center for Next Generation Chemical EcologyNIH: GM057440, NIAID R01Al137078 Formas: 2019-01590 Department of Defense: W81XWH-18-1-0732 Formas: 2019-01590
We thank Titus Farkas, Esther Evans, and Sophia Friedrich for assisting with behavioral experiments and mosquito rearing. Special thanks to Matthew De-Gennaro and Leslie B. Vosshall for providing mosquito strains. We thank Evolva AG (now part of Danstar Ferment AG) for kindly providing nootkatone. We thank Global Health Labs, Inc and Photonic Sentry Labs for the kind dona-tion of the Photonic Fence Monitoring Device. M.C.S., M.F.T., D.-D.Z., and R.I. were supported by the Max Planck Center for Next Generation Chemical Ecology, while K.D. and F.A. received funding from the NIH (GM057440) . N.M. ac-knowledges support from Formas (2019-01590) . C.J.P. and A.A. were supported by grants from the NIH (NIAID R01Al137078) and the Department of Defense (W81XWH-18-1-0732) .
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:001407737500001
- Scopus ID
- 2-s2.0-85213545448
- Other Identifier
- 991021985086504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology