Identification of a developmentally regulated Schistosoma mansoni serine protease homologous to mouse plasma kallikrein and human factor I

Abstract

The isolation of 2 genomic clones has allowed us to further characterize a Schistosoma mansoni serine protease designated SmSP1. The deduced amino acid sequence (248aa) considered as a 'light chain' encoding the active site, presents significant homologies with mouse plasma kallikrein and human factor I light chain. The secondary structure of SmSP1 'light chain' is correctly predicted and may be sufficient by itself to constitute an active enzyme. The biological function of SmSP1 is unknown, however, the homology with 2 serine proteases suggests that SmSP1 may play a role in the evasion of the host immune response. This is supported by the presence of the native protein corresponding to SmSP1 particularly in schistosomula released products (SRP) and in male dorsal spines. The expression of this enzyme is differentially regulated throughout the parasite life-cycle. However, infected animals with S. mansoni did not produce specific antibodies to recombinant SmSP1. The lack of such response could be advantageous to the parasite by protecting itself from host effector mechanisms.

Trypsin- and Chymotrypsin-Like Serine Proteases in Schistosoma mansoni – ‘The Undiscovered Country’

“…The five remaining SmSP genes, including the previously sequenced and partially characterized SmSP1 [13], [14], were cloned and sequenced. The other four gene sequences named SmSP2 through SmSP5 (Table 1) were significantly corrected and re-annotated in the primary database ( S. mansoni GeneDB) due to various sequence inaccuracies.…”

“…The sequences of SmSP2 through SmSP5 were deposited into the GenBank as KF510120, KF510121, KF510122, KF939306, respectively. The sequence of SmSP1 defined here was also deposited (KF535923) because of sequence differences from the original description (CAA09691 [13]) and from the information in S. mansoni GeneDB (Smp_030350; Figure S1). A search of the Schistosoma japonicum genome [44] indicates that orthologs for each of the SmSPs are present; SjSP1 (GeneDB Sjp_0012180, GenBank N/A), SjSP2 (Sjp_0100980, CAX74751), SjSP3 (Sjp_0023390, CAX73257), SjSP4 (Sjp_0047680, N/A) and SjSP5 (Sjp_0114710, CAX73292).…”

“…Among these, SmSP1 ( S. mansoni serine protease 1, GenBank AJ011561), has been partially described [13], [14]. The open reading frame (ORF) of SmSP1 comprises two non-proteolytic domains, followed by a C-terminal trypsin protease domain.…”

“…The open reading frame (ORF) of SmSP1 comprises two non-proteolytic domains, followed by a C-terminal trypsin protease domain. Expression of the trypsin domain (mRNA and protein) was noted in adult worms with a significant accumulation in the tegument (surface) of males [13]. Another SmSP was identified (under TC16843 code) by microarray analysis with a remarkably elevated expression in post-infective larvae (schistosomula) that had been maintained in vitro [23].…”

“…In addition to SmSP1, we identified and re-annotated four distinct SmSPs in the S. mansoni GeneDB genome database [25], [26] and term them SmSP2 through SmSP5 according to a previous terminology [13]. The data reveal intriguing expression profiles and phylogenetic relationships that stimulate further study of the individual proteases involved, and their contributions to modulating host physiology.…”