A cDNA encoding a pepsinogen-like, aspartic protease from the human roundworm parasite Strongyloides stercoralis.

Using degenerate oligonucleotide primers based on conserved active site residues, we have isolated a cDNA encoding an aspartic protease from the nematode parasite Strongyloides stercoralis, an important, enteric pathogen of humans. cDNAs encoding the aspartic protease were isolated from the infective, third stage larvae of the parasite as well as from free-living, rhabditiform larvae. Based on comparisons of other aspartic proteases, the cDNA encoded a short signal peptide, an enzyme pro-segment of 35 amino acid residues, and mature enzyme of 337 residues. Homology alignments using the proenzyme sequence showed that the novel S. stercoralis zymogen was 36% identical to human pepsinogen A and 36% identical to pepsinogen C (progastricin) from humans and macaques. Phylogenetic analyses using the Phylip program and analysis of Glx/Asx and Leu/Ile ratios indicated that the proenzyme was closely related to pepsinogen A-like enzymes from the free-living nematode Caenorhabditis elegans and Haemonchous contortus, a nematode parasite of the gastro-intestinal tract of sheep. We have termed this novel enzyme strongyloidespepsin.