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In vitro characterization of glutathione transferases from Sarcoptes scabiei

Molin, Eva U. (2009). In vitro characterization of glutathione transferases from Sarcoptes scabiei. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2009:80
ISBN 978-91-576-7427-2
[Doctoral thesis]

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Abstract

The mite Sarcoptes scabiei causes sarcoptic mange, or scabies, a disease that affects both animals and humans worldwide. The ectoparasite not only causes suffering in the host but also financial losses in e.g. pig herds. Infections can be cured with acaricides but treatment failures have been reported. Very little is known about drug detoxification in S. scabiei, and hence more information on underlying enzymatic mechanisms could prolong the lifespan of acaricides used in treatment of both animals and humans. The aim of this thesis was to characterize glutathione transferases (GSTs) from S. scabiei, investigate their possible involvement in resistance development and their potential as antigens in serology. GSTs are multifunctional enzymes with fundamental roles in the cellular detoxification, and these enzymes have been linked to drug resistance in various organisms. GSTs have also been suggested to confer acaricide resistance in S. scabiei. The first Delta GST occurring outside insects was identified, and phylogenetically classified. The crystal structure of this GST was also determined, which was the first Acari (mites and ticks) GST structure. The 3D-structures of two other Delta GSTs were predicted using homology modeling. Possible binding modes between the three Delta GSTs and various acaricides and the synergist diethyl maleate (DEM) were investigated using docking studies. Recombinant versions of the Delta GSTs and three Mu GSTs were biochemically characterized under steady-state conditions, and inhibition analyses with various acaricides and DEM were conducted. Additionally, the potential of the GSTs as antigens in serology was investigated. The results showed that all S. scabiei GSTs, except one, were catalytically active and significantly inhibited by various acaricides. However none of the GSTs were good antigens for serology. The docking studies showed that S. scabiei GSTs could metabolize or bind various acaricides, hence strengthening the suggestion that GSTs might confer resistance to acaricides in S. scabiei.

Authors/Creators:Molin, Eva U.
Title:In vitro characterization of glutathione transferases from Sarcoptes scabiei
Year of publishing :2009
Volume:2009:80
Number of Pages:87
Papers/manuscripts:
NumberReferences
ALLI. EU Pettersson, EL Ljunggren, DA Morrison & JG Mattsson. Functional analysis and localisation of a delta-class glutathione S-transferase from Sarcoptes scabiei. International Journal for Parasitology 35, 39-48. II. EU Molin & JG Mattsson. Effect of acaricides on the activity of glutathione transferases from the parasitic mite Sarcoptes scabiei. Parasitology 135, 115-123. III. EU Molin, R Friemann, M Ingelman, F Söderbom & JG Mattsson. Structure-function studies of Sarcoptes scabiei glutathione transferases: Modelling of various acaricides and the synergist diethyl maleate to three Delta GSTs. Manuscript.
Place of Publication:Uppsala
ISBN for printed version:978-91-576-7427-2
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agrovoc terms:sarocoptes scabiei, glutathione, acaricide, lindane, permethrin, inhibition, immunology
Keywords:Sarcoptes scabiei, GST, glutathione, resistance, acaricide, ivermectin, lindane, permethrin, inhibition, crystal structure
URN:NBN:urn:nbn:se:slu:epsilon-3017
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-3017
ID Code:2160
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
Deposited By: Eva Molin
Deposited On:17 Nov 2009 00:00
Metadata Last Modified:02 Dec 2014 10:16

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