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Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

ABSTRACT: We have cloned and identified the major cuticular glycoprotein (gp29) of lymphatic filarial nematode parasites as a homolog of the antioxidant enzyme glutathione peroxidase. The derived amino acid sequence predicted a protein of 25.8 kDa, with an amino-terminal hydrophobic signal peptide and two sites for N-linked glycosylation, consistent with the documented properties of gp29. Transcription of a full-length cDNA in an SP65 vector and subsequent translation of the RNA in reticulocyte lysates in vitro generated a protein of 27 kDa, which was glycosylated upon the addition of pancreatic microsomal membranes. A postulated role for this secreted enzyme could be inhibition of the oxidative burst of leukocytes and neutralization of secondary products of lipid peroxidation, thus providing one explanation for the resistance of these parasites to immune effector mechanisms and their persistence in the mammalian host.

SUBMITTER: Cookson E

PROVIDER: S-EPMC49392 | biostudies-other | 1992 Jul

REPOSITORIES: biostudies-other

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Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

Cookson E E Blaxter M L ML Selkirk M E ME

Proceedings of the National Academy of Sciences of the United States of America 19920701 13

We have cloned and identified the major cuticular glycoprotein (gp29) of lymphatic filarial nematode parasites as a homolog of the antioxidant enzyme glutathione peroxidase. The derived amino acid sequence predicted a protein of 25.8 kDa, with an amino-terminal hydrophobic signal peptide and two sites for N-linked glycosylation, consistent with the documented properties of gp29. Transcription of a full-length cDNA in an SP65 vector and subsequent translation of the RNA in reticulocyte lysates in ...[more]

PMID: 1631065

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Project description:Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of ?6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained by the inability of the human-parasitic species to complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages and identifications of host proteins associated with first-stage larvae (microfilariae) in the blood. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature microfilariae, released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterized members of the transthyretin-like protein family. Furthermore, biotin labeling revealed that redox proteins and enzymes involved in purinergic signaling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the human-infective filarial nematode Brugia malayi (reported previously in three independent published studies) identified differences that suggest a considerable underlying diversity of potential immunomodulators. The molecules identified in L. sigmodontis excretory-secretory products show promise not only for vaccination against filarial infections, but for the amelioration of allergy and autoimmune diseases.

Project description:Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of approximately 6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained because the human-parasitic species cannot complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature first-stage larvae (microfilariae), released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterised members of the transthyretin-like protein family. Furthermore, biotin labelling revealed that redox proteins and enzymes involved in purinergic signalling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the human–infective filarial nematode Brugia malayi (reported previously in three independent published studies) identified differences that suggest a considerable underlying diversity of potential immunomodulators. The molecules identified in L. sigmodontis excretory-secretory products show promise not only for vaccination against filarial infections, but for the amelioration of allergy and autoimmune diseases.

Dataset Information

Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

Publications

Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

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