Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum

Bin Zhan, Sen Liu, Samirah Perally, Jian Xue, Ricardo Fujiwara, Peter Michael Brophy, Shuhua Xiao, Yueyuan Liu, Jianjun Feng, Angela Williamson, Yan Wang, Lilian L. Bueno, Susana Mendez, Gaddam Goud, Jeffrey M. Bethony, John M. Hawdon, Alex Loukas, Karen Jones, Peter J. Hotez

Research output: Contribution to journalArticlepeer-review

98 Citations (SciVal)

Abstract

We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection.
Original languageEnglish
Pages (from-to)6903-6911
Number of pages9
JournalInfection and Immunity
Volume73
Issue number10
DOIs
Publication statusPublished - Oct 2005

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