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

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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Zhan B,Liu S,Perally S,Xue J,Fujiwara R,Brophy P,Xiao S,Liu Y,Feng J,Williamson A,Wang Y,Bueno LL,Mendez S,Goud G,Bethony JM,Hawdon JM,Loukas A,Jones K,Hotez PJ

doi

10.1128/IAI.73.10.6903-6911.2005

keywords:

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

6903-11

issue

10

eissn

0019-9567

issn

1098-5522

pii

73/10/6903

journal_volume

73

pub_type

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