Dissertation
Controlling wombat mange by targeting scabies ligand-gated chloride channels
University of the Sunshine Coast, Queensland
Doctor of Philosophy, University of the Sunshine Coast, Queensland
2024
DOI:
https://doi.org/10.25907/00869
Abstract
Sarcoptes scabiei, the microscopic burrowing mite responsible for sarcoptic mange, affects approximately 150 mammalian species across the world. In Australia, this disease is particularly severe in bare-nosed wombats (Vombatus ursinus), while also impacting both native and introduced wildlife species. There are currently several acaricides available to treat sarcoptic mange, including ivermectin, moxidectin and fluralaner, which target invertebrate ligand-gated chloride channels (LGCCs) activated by GABA or glutamate. However, treatment of wildlife diseases often faces challenges due to insufficient understanding of pharmacokinetic and pharmacodynamic interactions between acaricides, parasites, and hosts. Critical knowledge gaps in acaricide treatment of sarcoptic mange include: (i) There is no baseline information on the in vitro responses of S. scabiei to fluralaner; (ii) The physiological LGCC targets of the acaricides in S. scabiei remain uncharacterised; (iii) The mechanism of drug resistance in S. scabiei remain unexplored; and (iv) There is no comprehensive sequencing of S. scabiei LGCC genes from wild wombat populations for detecting genetic variants associated with acaricide resistance. My PhD research project addresses these questions through pharmacological, molecular and genetic characterisation of the LGCC acaricide targets in S. scabiei. I investigated in vitro drug sensitivity of fluralaner and a formulation vehicle (orange oil) against S. scabiei providing insights into their baseline efficacy, which confirmed their acaricidal properties and further support potential suitability of orange oil as a formulation vehicle for fluralaner. Genetic characterisation of the S. scabiei LGCCs was accomplished by amplification of full-length cDNAs using recently published high-quality genome data. I have identified 12 predicted LGCC genes in S. scabiei and explored their phylogenetics, assessing their potential roles in acaricide actions, resistance mechanisms and physiology. I also investigated the genetic diversity of selected S. scabiei LGCC genes sourced from wombat populations from different locations within Australia, discovering variants that could potentially have impacts on acaricide binding to LGCCs. These studies represent the first phenotypic and genetic investigations of LGCCs in S. scabiei, offering valuable information that may guide treatment and provide baseline data for monitoring acaricide resistance. This 'ground-up' approach has also created unique opportunities for engagement with wildlife carers aimed at enhancing treatment success.
Details
- Title
- Controlling wombat mange by targeting scabies ligand-gated chloride channels
- Authors
- Kotaro Takano - University of the Sunshine Coast, Queensland, External
- Contributors
- Robert Harvey (Principal Supervisor) - University of the Sunshine Coast, Queensland, School of HealthKate Mounsey (Co-Supervisor) - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
- Awarding institution
- University of the Sunshine Coast, Queensland
- Degree awarded
- Doctor of Philosophy
- Publisher
- University of the Sunshine Coast, Queensland
- DOI
- 10.25907/00869
- Organisation Unit
- School of Health
- Language
- English
- Record Identifier
- 991058098902621
- Output Type
- Dissertation
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