Mr 26,000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase.

Abstract

authors request that the following correction be noted. Recent nucleotide sequence analysis has established that a C residue was omitted at position 628 of the Sj26 cDNA sequence presented in Fig. 2. The amended nucleotide sequence and the altered prediction of the COOH-terminal structure of Sj26 are given below. This correction does not otherwise affect the conclusions of the paper. ABSTRACT Mice of the inbred strain 129/J bred at this Institute (WEHI 129/J) are relatively resistant to chronic infection with the parasitic helminth Schistosomajaponicum. In contrast to more permissive mouse strains such as BALB/c, the WEHI 129/J mice are high responders to a Mr 26,000 adult worm antigen designated Sj26. Cloned cDNAs corresponding to Sj26 have been identified in a S. japonicum phage Xgtll amp3 expression library, and their nucleotide sequences have been deduced. The predicted amino acid sequence of the antigen specified by these cDNAs shows striking homology with class it isozymes of mammalian glutathione S-transferases (RX:glutathione R-transferase, EC 2.5.1.18). Extracts of adult worms contain glutathione S-transferase activity, and affinity chromatography of enzyme activity on glutathione columns leads to the purification of a Mr 26,000 molecule that comigrates with Sj26. Although vaccination studies in mice with a .3-galactosidase-Sj26 fusion protein from Escherichia coli are encouraging, more immunogenic preparations of the antigen are likely to be required to establish the utility of Sj26 as a model vaccine.

Conformational stability of pGEX‐expressed Schistosoma japonicum glutathione S‐transferase: A detoxification enzyme and fusion‐protein affinity tag

“…The pGEX-2T plasmid (Pharmacia) was used to overexpress the Sj26GST in E. coli strain JM109 (Smith et al, 1986;Smith & Johnson, 1988). Once the cells had reached an optical density of 0.6-1.0 in Luna-Bertani culture medium containing 50 pg/mL ampicillin, isopropyl-P-D-thiogalactoside was added at a final concentration of 1 mM to induce overexpression of Sj26GST.…”

“…The glutathione-conjugates have greater solubility in water, facilitating their export from the cell, where they are metabolized via the mercapturate pathway and eventually excreted. Sj26GST is also a nonsubstrate ligand-binding protein capable of sequestering hostderived heme in the parasitic helminth, thus reducing hemeinduced oxidative damage and the formation of toxic haematin crystals (Smith et al, 1986;McTigue et al, 1995).…”

Schistosoma mansonicercarial elastase (SmCE): differences in immunogenic properties of native and recombinant forms

“…Although GSTs were first identified as vaccine candidates by Smith et al (1986), Sj26GST, unlike SmGST and ShGST, was shown to have 'unsatisfactory' vaccinating potential since it induced variable/inconsistent protective immune responses to S. japonicum in different mouse strains (Davern et al 1987;Scott and McManus, 2000). In a previous research, when used as a control for immunization with another recombinant protein fused with SjGST, GST derived from S. japonicum was ineffective in reducing parasite burdens in a murine challenge model of S. mansoni (Schechtman et al 2001).…”

Inhibition of Filarial Glutathione-S-transferase by various classes of compounds and their evaluation as novel antifilarial agents

“…Helminth GST(s) appear to bind a range of hydrophobic ligands, including hematin related com- pounds, bile acids, unsaturated fatty acids and plant phenols. Binding could also be a passive detoxification mechanism, as has been suggested for the interaction of hematin with S. japonicum GST (Smith et al, 1986). This may indicate that, as proposed for a number of mammalian hepatic GST(s) (Ketterer et al, 1988), helminth GST(s) are general binding proteins involved in the transport of hydrophobic ligands.…”