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Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito Anopheles gambiae

Ito, Ryo, Kamiya, Masaki, Takayama, Koichi, Mori, Sumito, Matsumoto, Rei, Takebayashi, Mayuka, Ojima, Hisanori, Fujimura, Shota, Yamamoto, Haruki, Ohno, Masayuki, Ihara, Makoto, Okajima, Toshihide, Yamashita, Atsuko, Colman, Fraser, Lycett, Gareth ORCID: https://orcid.org/0000-0002-2422-053X, Sattelle, David B. and Matsuda, Kazuhiko (2024) 'Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito Anopheles gambiae'. Open Biology, Vol 14, Issue 7.

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Abstract

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agβ1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agβ1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control.

Item Type: Article
Subjects: QX Parasitology > QX 20 Research (General)
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1098/rsob.240057
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 25 Jul 2024 13:29
Last Modified: 25 Jul 2024 13:29
URI: https://archive.lstmed.ac.uk/id/eprint/24989

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