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Title: Investigating the molecular basis of resistance and pyrethroid selectivity at acarine sodium channels
Author: Blockley, Alix Dawn
ISNI:       0000 0004 6353 0789
Awarding Body: Birkbeck, University of London
Current Institution: Birkbeck (University of London)
Date of Award: 2017
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Many acarine (tick and mite) species are ectoparasites of humans, livestock and domestic pets, where they spread disease and impact adversely on health. They are normally controlled through the application of acaricides; however, the prolonged use of individual compounds has resulted in many species developing resistance to specific pesticides. This thesis describes investigations into the molecular properties that determine the resistance to and selectivity of pyrethroids, an important class of pesticides that act on the voltage-gated sodium channels (VGSCs) of arthropod neurons. Comparison of insect and acarine VGSC sequences, coupled with molecular modelling studies, have identified a residue at amino-acid position 933 (M. domestica numbering) found within a putative pyrethroid binding pocket that may contribute to a greater selectivity of pyrethroids with comparatively larger halogenated groups for acarine VGSCs compared to those of insects. This is due to the presence of a smaller glycine residue at position 933 in acarine channels, compared to a cysteine residue in insect channels, which may enhance the binding of such pyrethroids (O'Reilly et al., 2014). This model is supported by the findings of Jonsson et al 2010, that R. microplus cattle ticks carrying the amino acid substitution G933V, are resistant to the pyrethroid flumethrin, which has a comparatively larger halogenated group, but not the pyrethroid cypermethrin, which has a comparatively smaller halogenated group. Work in this thesis describes progress made in the investigation of such specificity; involving sequencing studies, two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes involving insect and acarine VGSCs, and whole arthropod bioassays. While this work cannot conclusively disprove the model proposed by O’Reilly et al 2014, it suggests that the mechanisms of selectivity for pyrethroids in arthropods may involve the interplay of several factors, rather than being solely based upon structural variations in their VGSCs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available