A CDNA-ENCODING A PEPSINOGEN-LIKE, ASPARTIC PROTEASE FROM THE HUMAN ROUNDWORM PARASITE STRONGYLOIDES-STERCORALIS

Using degenerate oligonucleotide primers based on conserved active sit e residues, we have isolated a cDNA encoding an aspartic protease from the nematode parasite Strongyloides stercoralis, an important, enteri c pathogen of humans. cDNAs encoding the aspartic protease were isolat ed from the infective, third stage larvae of the parasite as well as f rom free-living, rhabditiform larvae. Based on comparisons of other as partic proteases, the cDNA encoded a short signal peptide, an enzyme p ro-segment of 35 amino acid residues, and mature enzyme of 337 residue s. Homology alignments using the proenzyme sequence showed that the no vel 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/A sx and Leu/Ile ratios indicated that the proenzyme was closely related to pepsinogen A-like enzymes from the free-living nematode Caenorhabd itis elegans and Haemonchous contortus, a nematode parasite of the gas tro-intestinal tract of sheep. We have termed this novel enzyme strong yloidespepsin. (C) 1998 Elsevier Science B.V. All rights reserved.