title: A new amino-acid substitution in acetylcholinesterase 1 confers insecticide resistance to Culex pipiens mosquitoes from Cyprus.
abstract: In insects, selection of insecticide-insensitive acetylcholinesterase (AChE) is a very common resistance mechanism. Mosquitoes possess both AChE1 and AChE2 enzymes and insensitivity is conferred by single amino-acid changes located near the active site of the synaptic AChE1. Only two positions have been reported so far to be involved in resistance, suggesting a very high structural constraint of the AChE1 enzyme. In particular, the G119S substitution was selected in several mosquitoes' species and is now largely spread worldwide. Yet, a different type of AChE1 insensitivity was described 10 years ago in a Culex pipiens population collected in Cyprus in 1987 and fixed thereafter as the ACE-R strain. We report here the complete amino-acid sequence of the ACE-R AChE1 and show that resistance is associated with a single Phe-to-Val substitution of residue 290, which also lines the active site. Comparison of AChE1 activities of the recombinant F290V protein and ACE-R mosquito extracts confirmed the causal role of the substitution in insensitivity. Biochemical characteristics of the mutated protein indicated that the resistance level varies with the insecticide used. A molecular diagnosis test was designed to detect this mutation and was used to show that it is still present in Cyprus Island.
authors.affiliation: Laboratoire Génétique et Environnement Institut des Sciences de l'Evolution (UMR CNRS 5554), Université de Montpellier II (C.C. 065), F-34095 Montpellier cedex 05, France.
authors.forename: Haoues
authors.initials: H
authors.lastname: Alout
authors.forename: Arnaud
authors.initials: A
authors.lastname: Berthomieu
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjivassilis
authors.forename: Mylène
authors.initials: M
authors.lastname: Weill
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D019943:Amino Acid Substitution; D000818:Animals; D003465:Culex / Q000201:enzymology / Q000235:genetics*; D003535:Cyprus; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides; D009154:Mutation; D010649:Phenylalanine; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D014633:Valine
chemical_list: D007306:Insecticides; D011994:Recombinant Proteins; D010649:Phenylalanine; D000110:Acetylcholinesterase; D014633:Valine