Acetylcholinesterase (AChE) insensitive to organophosphate and carbamate insecticides has been identified as a major resistance mechanism in numerous arthropod species. However, the associated genetic changes have been reported in the AChE genes from only three insect species; their role in conferring insecticide insensitivity has been confirmed, using functional expression, only for those in Drosophila melanogaster. The housefly, Musca domestica, was one of the first insects shown to have this mechanism; here we report the occurrence of five mutations (Val-180 → Leu, Gly-262 → Ala, Gly-262 → Val, Phe-327 → Tyr and Gly-365 → Ala) in the AChE gene of this species that, either singly or in combination, confer different spectra of insecticide resistance. The baculovirus expression of wild-type and mutated housefly AChE proteins has confirmed that the mutations each confer relatively modest levels of insecticide insensitivity except the novel Gly-262 → Val mutation, which results in much stronger resistance (up to 100-fold) to certain compounds. In all cases the effects of mutation combinations are additive. The mutations introduce amino acid substitutions that are larger than the corresponding wild-type residues and are located within the active site of the enzyme, close to the catalytic triad. The likely influence of these substitutions on the accessibility of the different types of inhibitor and the orientation of key catalytic residues are discussed in the light of the three-dimensional structures of the AChE protein from Torpedo californica and D. melanogaster.
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October 2001
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Research Article|
September 24 2001
Identification and characterization of mutations in housefly (Musca domestica) acetylcholinesterase involved in insecticide resistance
Sinéad B. WALSH;
Sinéad B. WALSH
∗Biological and Ecological Chemistry Department, IACR-Rothamsted, Harpenden, Herts. AL5 2JQ, U.K.
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Tracey A. DOLDEN;
Tracey A. DOLDEN
∗Biological and Ecological Chemistry Department, IACR-Rothamsted, Harpenden, Herts. AL5 2JQ, U.K.
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Graham D. MOORES;
Graham D. MOORES
∗Biological and Ecological Chemistry Department, IACR-Rothamsted, Harpenden, Herts. AL5 2JQ, U.K.
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Michael KRISTENSEN;
Michael KRISTENSEN
†Danish Pest Infestation Laboratory, Skovbrynet 14, DK-2800 Lyngby, Denmark
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Terence LEWIS;
Terence LEWIS
‡Zeneca Agrochemicals, Jealott's Hill Research Station, Bracknell, Berks. RG42 6ET, U.K.
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Alan L. DEVONSHIRE;
Alan L. DEVONSHIRE
∗Biological and Ecological Chemistry Department, IACR-Rothamsted, Harpenden, Herts. AL5 2JQ, U.K.
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Martin S. WILLIAMSON
Martin S. WILLIAMSON
1
∗Biological and Ecological Chemistry Department, IACR-Rothamsted, Harpenden, Herts. AL5 2JQ, U.K.
1To whom correspondence should be addressed (e-mail martin.williamson@bbsrc.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 26 2001
Revision Received:
July 02 2001
Accepted:
July 27 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 359 (1): 175–181.
Article history
Received:
March 26 2001
Revision Received:
July 02 2001
Accepted:
July 27 2001
Citation
Sinéad B. WALSH, Tracey A. DOLDEN, Graham D. MOORES, Michael KRISTENSEN, Terence LEWIS, Alan L. DEVONSHIRE, Martin S. WILLIAMSON; Identification and characterization of mutations in housefly (Musca domestica) acetylcholinesterase involved in insecticide resistance. Biochem J 1 October 2001; 359 (1): 175–181. doi: https://doi.org/10.1042/bj3590175
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