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Title: Molecular basis of pyrethroid sensitivity and resistance
Author: Burton, Mark James
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Pyrethroid insecticides remain one of the most widely used classes of insecticides yet resistance threatens their effective continued use. Recently efforts have been applied to understand the genetics and physiology of known mechanisms of resistance. Key mutations of the insect voltage gated sodium channel, such as L1014F, have been implicated in conferring resistance in a number of pest insect species. Two other substitutions of the Ll014 locus have also been reported in the field, l1014S and l1014H. In this study L1014 modified Drosophila para VGSCs were expressed in Xenopus oocytes and their properties examined electrophysiologically using two-electrode voltage-clamp. This revealed significant depolarising shifts in the half activation voltage (V50.act ) from -17.3 mV (wild-type) to -13.1 mV and -13.5 mV for L1014F and L1014H respect ively. whereas the l1014S mutation caused no significant shift in V50.act but its current decayed significantly faster than the wild-type channel. Treatment of the wildtype channel with deltamethrin (>1 nM), permethrin (>30 nM) or DichloroDiphenyl- Trichloroethane (DDT) (>1 uM) resulted in hyperpolarizing shifts in V50.act. Deltamethrin, permethrin and DDT also produced "tail currents" with EC50S of 0.043, 0.40 and 61 uM and maximum modifications of 825, 326 and 6% respectively. L1014F provided a high level of resistance against all insecticides for both measured parameters. L1014H most effectively combated deltamethrin induced tail currents while L1014S strongly resisted the large DDT induced shifts in V50.act. We conclude that L1014H and L1014S may have arisen through continued exposure to specific pyrethroids and DDT respectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available