Small-Molecule Agonists of Ae. aegypti Neuropeptide Y Receptor Block Mosquito Biting.
Aedes aegypti
CRISPR-Cas9
Zika
blood-feeding
dengue
feeding
high-throughput small-molecule screen
host-seeking behavior
mosquito
neuropeptide Y
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 02 2019
07 02 2019
Historique:
received:
16
08
2018
revised:
17
10
2018
accepted:
03
12
2018
entrez:
9
2
2019
pubmed:
9
2
2019
medline:
4
12
2019
Statut:
ppublish
Résumé
Female Aedes aegypti mosquitoes bite humans to obtain blood to develop their eggs. Remarkably, their strong attraction to humans is suppressed for days after the blood meal by an unknown mechanism. We investigated a role for neuropeptide Y (NPY)-related signaling in long-term behavioral suppression and discovered that drugs targeting human NPY receptors modulate mosquito host-seeking. In a screen of all 49 predicted Ae. aegypti peptide receptors, we identified NPY-like receptor 7 (NPYLR7) as the sole target of these drugs. To obtain small-molecule agonists selective for NPYLR7, we performed a high-throughput cell-based assay of 265,211 compounds and isolated six highly selective NPYLR7 agonists that inhibit mosquito attraction to humans. NPYLR7 CRISPR-Cas9 null mutants are defective in behavioral suppression and resistant to these drugs. Finally, we show that these drugs can inhibit biting and blood-feeding on a live host, suggesting a novel approach to control infectious disease transmission by controlling mosquito behavior. VIDEO ABSTRACT.
Identifiants
pubmed: 30735632
pii: S0092-8674(18)31587-3
doi: 10.1016/j.cell.2018.12.004
pmc: PMC6369589
mid: NIHMS1516135
pii:
doi:
Substances chimiques
Receptors, Neuropeptide Y
0
Small Molecule Libraries
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
687-701.e5Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC014247
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000043
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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