Proteomic analysis of secretory products from the model gastrointestinal nematode Heligmosomoides polygyrus reveals dominance of Venom Allergen-Like (VAL) proteins

The intestinal helminth parasite, Heligmosomoides polygyrus bakeri offers a tractable experimental model for human hookworm infections such as Ancylostoma duodenale and veterinary parasites such as Haemonchus contortus. Parasite excretory–secretory (ES) products represent the major focus for immunological and biochemical analyses, and contain immunomodulatory molecules responsible for nematode immune evasion. In a proteomic analysis of adult H. polygyrus secretions (termed HES) matched to an extensive transcriptomic dataset, we identified 374 HES proteins by LC–MS/MS, which were distinct from those in somatic extract HEx, comprising 446 identified proteins, confirming selective export of ES proteins. The predominant secreted protein families were proteases (astacins and other metalloproteases, aspartic, cysteine and serine-type proteases), lysozymes, apyrases and acetylcholinesterases. The most abundant products were members of the highly divergent venom allergen-like (VAL) family, related to Ancylostoma secreted protein (ASP); 25 homologues were identified, with VAL-1 and -2 also shown to be associated with the parasite surface. The dominance of VAL proteins is similar to profiles reported for Ancylostoma and Haemonchus ES products. Overall, this study shows that the secretions of H. polygyrus closely parallel those of clinically important GI nematodes, confirming the value of this parasite as a model of helminth infection.

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► We identify 374 proteins secreted by adult worms of the model nematode parasite Heligmosomoides polygyrus.
► Multiple proteases, lysozymes, apyrases and acetylcholinesterase were identified.
► The dominant gene family in the secretome are members of the venom allergen-like (VAL) family of no known function.
► The secretion of VAL proteins and enzymes is also found in secretomes of major human and veterinary nematodes.
► Up to 90 novel gene products were found to be secreted, all bearing signal peptides, by the adult parasites.