Proteomic analysis of glutathione transferases from the liver fluke parasite,Fasciola hepatica

Abstract

The parasite Fasciola hepatica causes major global disease of livestock, with increasing reports of human infection. Vaccine candidates with varying protection rates have been identified by pre-genomic approaches. As many candidates are part of protein superfamilies, sub-proteomics offers new possibilities to systematically reveal the relative importance of individual family proteins to vaccine formulations within populations. The superfamily glutathione transferase (GST) from liver fluke has phase II detoxification and housekeeping roles, and has been shown to contain protective vaccine candidates. GST were purified from cytosolic fractions of adult flukes using glutathione- and S-hexylglutathione-agarose, separated by 2-DE, and identified by MS/MS, with the support of a liver fluke EST database. All previously described F. hepatica GST isoforms were identified in 2-DE. Amongst the isoforms mapped by 2-DE, a new GST, closely related to the Sigma class enzymes is described for the first time in the liver fluke. We also describe cDNA encoding putative Omega class GST in F. hepatica.

Differential Activation of Diverse Glutathione Transferases of Clonorchis sinensis in Response to the Host Bile and Oxidative Stressors

“…However, as is shown in Figures 1D and 1E, secretion of 28 kDa Cs28σGST3 species appeared to be substantially decreased (up to 95%) in the bile stimulated ESP, while that of immunologically-related high-molecular weight proteins were profoundly augmented as bile concentrations increased. This is a unique finding observed for the first time with C. sinensis ESP, but not with other trematode such as F. hepatica and O. viverrini , which also reside in the mammalian bile duct [13], [16], [34]. We purified the global CsGST fractions using GSH-matrix and observed that the 85 kDa protein shared peptide fragments with the 28 kDa Cs28σGST3, thus representing a genuine Cs28σGST3.…”

Major Secretory Antigens of the Helminth Fasciola hepatica Activate a Suppressive Dendritic Cell Phenotype That Attenuates Th17 Cells but Fails To Activate Th2 Immune Responses

“…At least seven speciesindependent classes of cytosolic GST are known and may be distinguished from each other on the basis of substrate specificity and inhibitor sensitivity (45,47). Three GST classes, representing at least six distinct enzymes, have been identified in F. hepatica (10,45). We have not determined if enzyme activity is important for the activation of DCs described here.…”

Towards Delineating Functions within the Fasciola Secreted Cathepsin L Protease Family by Integrating In Vivo Based Sub-Proteomics and Phylogenetics

“…A limited understanding of the Cat L protease sub-proteome may be hindering development of this vaccine candidate protein family [25]. A key consideration for vaccine development is to target functional components that are required for the survival of the parasite [26].…”