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The soluble glutathione transferase superfamily: role of Mu class in triclabendazole sulphoxide challenge in Fasciola hepatica

Authors
  • Stuart, Rebekah B.1
  • Zwaanswijk, Suzanne1
  • MacKintosh, Neil D.1
  • Witikornkul, Boontarikaan1
  • Brophy, Peter M.1
  • Morphew, Russell M.1
  • 1 Aberystwyth University,
Type
Published Article
Journal
Parasitology Research
Publisher
Springer-Verlag
Publication Date
Jan 27, 2021
Volume
120
Issue
3
Pages
979–991
Identifiers
DOI: 10.1007/s00436-021-07055-5
PMID: 33501588
PMCID: PMC7889535
Source
PubMed Central
Keywords
Disciplines
  • Helminthology - Original Paper
License
Unknown

Abstract

Fasciola hepatica (liver fluke), a significant threat to food security, causes global economic loss for the livestock industry and is re-emerging as a foodborne disease of humans. In the absence of vaccines, treatment control is by anthelmintics; with only triclabendazole (TCBZ) currently effective against all stages of F. hepatica in livestock and humans. There is widespread resistance to TCBZ and its detoxification by flukes might contribute to the mechanism. However, there is limited phase I capacity in adult parasitic helminths with the phase II detoxification system dominated by the soluble glutathione transferase (GST) superfamily. Previous proteomic studies have demonstrated that the levels of Mu class GST from pooled F. hepatica parasites respond under TCBZ-sulphoxide (TCBZ-SO) challenge during in vitro culture ex-host. We have extended this finding by exploiting a sub-proteomic lead strategy to measure the change in the total soluble GST profile (GST-ome) of individual TCBZ-susceptible F. hepatica on TCBZ-SO-exposure in vitro culture. TCBZ-SO exposure demonstrated differential abundance of FhGST-Mu29 and FhGST-Mu26 following affinity purification using both GSH and S-hexyl GSH affinity. Furthermore, a low or weak affinity matrix interacting Mu class GST (FhGST-Mu5) has been identified and recombinantly expressed and represents a new low-affinity Mu class GST. Low-affinity GST isoforms within the GST-ome was not restricted to FhGST-Mu5 with a second likely low-affinity sigma class GST (FhGST-S2) uncovered. This study represents the most complete Fasciola GST-ome generated to date and has supported the potential of subproteomic analyses on individual adult flukes. Supplementary Information The online version contains supplementary material available at 10.1007/s00436-021-07055-5.

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