Characterization of a novel glycosylated glutathione transferase of Onchocerca ochengi, closest relative of the human river blindness parasite

Clair Rose, Giorgio Praulins, Stuart D. Armstrong, Aitor Casas-Sanchez, Jem Davis, Gemma Molyneux, Cristina Yunta, Zenaida Stead, Mark Prescott, Samirah Perally, Anne Rutter, Benjamin L. Makepeace, E. James La Course*, Alvaro Acosta-Serrano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Filarial nematodes possess glutathione transferases (GSTs), ubiquitous enzymes with the potential to detoxify xenobiotic and endogenous substrates, and modulate the host immune system, which may aid worm infection establishment, maintenance and survival in the host. Here we have identified and characterized a σ class glycosylated GST (OoGST1), from the cattle-infective filarial nematode Onchocerca ochengi, which is homologous (99% amino acid identity) with an immunodominant GST and potential vaccine candidate from the human parasite, O. volvulus, (OvGST1b). Onchocerca ochengi native GSTs were purified using a two-step affinity chromatography approach, resolved by 2D and 1D SDS-PAGE and subjected to enzymic deglycosylation revealing the existence of at least four glycoforms. A combination of lectin-blotting and mass spectrometry (MS) analyses of the released N-glycans indicated that OoGST1 contained mainly oligomannose Man5GlcNAc2 structure, but also hybrid- and larger oligommanose-type glycans in a lower proportion. Furthermore, purified OoGST1 showed prostaglandin synthase activity as confirmed by Liquid Chromatography (LC)/MS following a coupled-enzyme assay. This is only the second reported and characterized glycosylated GST and our study highlights its potential role in host-parasite interactions and use in the study of human onchocerciasis.

Original languageEnglish (US)
Pages (from-to)1773-1784
Number of pages12
JournalParasitology
Volume146
Issue number14
DOIs
StatePublished - Dec 1 2019

Keywords

  • Detoxification
  • glycans
  • glycosylation
  • GSTs
  • immune modulation
  • Onchocerca
  • prostaglandin synthase

ASJC Scopus subject areas

  • Parasitology
  • Animal Science and Zoology
  • Infectious Diseases

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