期刊
PLOS NEGLECTED TROPICAL DISEASES
卷 12, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pntd.0006446
关键词
-
资金
- Ministry of Education, Youth and Sports of the Czech Republic [LD15101, LH15040, InterBioMed LO1302]
- Charles University in Prague [PROGRES Q25/LF1, UNCE 204017]
- Charles University Grant Agency, Czech Republic [1404317]
- US National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R21AI126296]
- NIH [R01 GM104659]
- [RVO 61388963]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM104659] Funding Source: NIH RePORTER
Background Serine proteases are important virulence factors for many pathogens. Recently, we discovered a group of trypsin-like serine proteases with domain organization unique to flatworm parasites and containing a thrombospondin type 1 repeat (TSR-1). These proteases are recognized as antigens during host infection and may prove useful as anthelminthic vaccines, however their molecular characteristics are under-studied. Here, we characterize the structural and proteolytic attributes of serine protease 2 (SmSP2) from Schistosoma mansoni, one of the major species responsible for the tropical infectious disease, schistosomiasis. Methodology/Principal findings SmSP2 comprises three domains: a histidine stretch, TSR-1 and a serine protease domain. The cleavage specificity of recombinant SmSP2 was determined using positional scanning and multiplex combinatorial libraries and the determinants of specificity were identified with 3D homology models, demonstrating a trypsin-like endopeptidase mode of action. SmSP2 displayed restricted proteolysis on protein substrates. It activated tissue plasminogen activator and plasminogen as key components of the fibrinolytic system, and released the vasoregulatory peptide, kinin, from kininogen. SmSP2 was detected in the surface tegument, esophageal glands and reproductive organs of the adult parasite by immunofluorescence microscopy, and in the excretory/secretory products by immunoblotting. Conclusions/Significance The data suggest that SmSP2 is secreted, functions at the host-parasite interface and contributes to the survival of the parasite by manipulating host vasodilatation and fibrinolysis. SmSP2 may be, therefore, a potential target for anti-schistosomal therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据