Schistosoma japonicum , S. mansoni , S. haematobium, S. intercalatum , and S. rodhaini : cysteine-class cathepsin activities in the vomitus of adult worms

Abstract

Vomitus from adults of five Schistosoma species was screened for biochemical homologues of the mammalian cysteine proteinases cathepsins B, H, and L. Bovine cathepsin B and rat cathepsin L served as references. Using the substrate Arg-NMec, a schistosome cathepsin H-like activity was never detected. All species degraded the cathepsin B substrate Z-Arg-Arg-NMec, but distinct species differences were observed with respect to pH optima and buffer preferences. The cathepsin B and L substrate Z-Phe-Arg-NMec was similarly degraded by all species, and activity was abolished by the cysteine proteinase inhibitor E-64. Preferences by vomitus proteinase activities for Z-Phe-Arg-NMec over Z-Arg-Arg-NMec were similar to or higher than those found for bovine cathepsin B but well below those observed for rat cathepsin L; also, the preferential cathepsin L inhibitor Z-Phe-PheCHN2 only partially inhibited proteinolytic activity. The results suggest the possible presence in vomitus of a minor cathepsin L-like activity and demonstrate a major cathepsin B-like activity that is biochemically variable between schistosome species.

Structural Basis for Inhibition of Cathepsin B Drug Target from the Human Blood Fluke, Schistosoma mansoni

“…This is congruent with the identification of SmCB1 as a major target for inhibition by K11777 during experimental therapy in a murine model of S. mansoni infection (15). Given the catalytic efficiency of SmCB1 against hemoglobin described here and being the major cysteine peptidase activity in the parasite (13,75), it might be anticipated that inhibition of this enzyme would impact the parasite's ability to thrive. Indeed, RNA interference of SmCB1 slowed the growth of the parasite both in culture and in an animal model of infection (14).…”

Private Selective Sweeps Identified from Next-Generation Pool-Sequencing Reveal Convergent Pathways under Selection in Two Inbred Schistosoma mansoni Strains

“…Simoes et al [61] previously described SNPs in the cysteine protease Cathepsin B vaccine target gene that are involved in significant conformation changes leading to an alteration in antibody binding to the protein. Variability among Schistosoma species at the biochemical level has been described earlier for cathepsin B-like activity [62]. Our results suggest that different selective pressures operated on this gene, and we propose that using this as a target for vaccine development could rapidly become inefficient in natural populations.…”

Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases

“…Expression increases in the parasite gut soon after skin penetration and schistosomular transformation corresponding to the initiation of blood feeding (Zerda et al, 1988). The peptidase was reported to be the major hemoglobin-digesting enzyme alongside another papain-like cysteine peptidase, cathepsin L1 (SmCL1), both of which are major proteins in worm soluble extracts and ESP (Day et al, 1995; Dalton et al, 1996; Caffrey et al, 1997; Brady et al, 1999a, b, 2000; Bogitsh et al, 2001). SmCL1 efficiently degrades human hemoglobin to absorbable dipeptides and amino acids and is localized to the gastrodermis and to the tegument of adult worms.…”