Mutations on M3 helix of Plutella xylostella glutamate-gated chloride channel confer unequal resistance to abamectin by two different mechanisms.
Abamectin is one of the most widely used avermectins for agricultural pests control, but the emergence of resistance around the world is proving a major threat to its sustained application. Abamectin acts by directly activating glutamate-gated chloride channels (GluCls) and modulating other Cys-loop ion channels. To date, three mutations occurring in the transmembrane domain of arthropod GluCls are associated with target-site resistance to abamectin: A309V in Plutella xylostella GluCl (PxGluCl), G323D in Tetranychus urticae GluCl1 (TuGluCl1) and G326E in TuGluCl3. To compare the effects of these mutations in a single system, A309V/I/G and G315E (corresponding to G323 in TuGluCl1 and G326 in TuGluCl3) substitutions were introduced individually into the PxGluCl channel. Functional analysis using Xenopus oocytes showed that the A309V and G315E mutations reduced the sensitivity to abamectin by 4.8- and 493-fold, respectively. In contrast, the substitutions A309I/G show no significant effects on the response to abamectin. Interestingly, the A309I substitution increased the channel sensitivity to glutamate by one order of magnitude (∼12-fold). Analysis of PxGluCl homology models indicates that the G315E mutation interferes with abamectin binding through a steric hindrance mechanism. In contrast, the structural consequences of the A309 mutations are not so clear and an allosteric modification of the binding site is the most likely mechanism. Overall the results show that both A309V and G315E mutations may contribute to target-site resistance to abamectin and may be important for the future prediction and monitoring of abamectin resistance in P. xylostella and other arthropod pests.
['Wang|Xingliang|X|', 'Puinean|Alin M|AM|', 'O Reilly|Andrias O|AO|', 'Williamson|Martin S|MS|', 'Smelt|Charles L C|CLC|', 'Millar|Neil S|NS|', 'Wu|Yidong|Y|']
D000595:Amino Acid Sequence D000818:Animals D018118:Chloride Channels D018698:Glutamic Acid D019476:Insect Proteins D007305:Insecticide Resistance D007306:Insecticides D007559:Ivermectin D008969:Molecular Sequence Data D009036:Moths D009154:Mutation D014982:Xenopus laevis
Glutamate-gated chloride channel Abamectin Target-site resistance Molecular modelling