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Role of elevated transcription of Glutathione S-Transferases (GSTS) in Pyrethroid Resistant Scabies Mites
Abstract

Role of elevated transcription of Glutathione S-Transferases (GSTS) in Pyrethroid Resistant Scabies Mites

C Pasay, Kate E Mounsey, L Arlian, M Morgan, D C Holt, B J Currie, Shelley F Walton and J McCarthy
58th American Society of Tropical Medicine and Hygiene Annual Meeting: Abstract Book, p.3
American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting, 58th (Washington, United States, 18-Nov-2009–22-Nov-2009)
2009
url
http://www.astmh.org/AM/Template.cfm?Section=Meeting_Archives&Template=/CM/ContentDisplay.cfm&ContentID=2310View
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Abstract

Medical Microbiology Public Health and Health Services
In northern Australia, 5% permethrin is widely used in community based treatment programs for control of endemic scabies. Increased in-vitro survival of human mites exposed to permethrin suggests emerging acaricide resistance. In this study, we used biochemical and molecular approaches to investigate the role of GSTs in mediating permethrin resistance, and evaluated the contribution of GST mediated detoxification as a mechanism of permethrin tolerance in human scabies mites. Comparison of GST activity in permethrin tolerant and sensitive mites showed a two-fold increase in enzymatic activity (p less than 0.0001). Quantitative real time PCR was then used to evaluate contribution of different scabies mite GST isoenzymes in permethrin resistant Sarcoptes scabiei var. canis, tolerant var. hominis and sensitive var. suis mites. Up regulation of three different GST transcripts was observed in resistant mites: μ1 (p less than 0.0001), δ 1 (p less than 0.0001) and δ 2 (p less than 0.001). In recent bioassays, a significantly increased in vitro survival was observed in S. Scabiei var. hominis exposed to permethrin compared to naïve S. scabiei var. suis (p less than 0.0001). The addition of the GST inhibitor diethyl maleate restored permethrin susceptibility, supporting a role for GST mediated detoxification in permethrin resistance. Altogether, these findings validate metabolic mechanisms as mediators of pyrethroid resistance in scabies and highlight the threat of emerging permethrin resistance to the treatment of this disease.

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