SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties.
SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties.
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DOI：
10.1371/journal.pntd.0006446
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发表时间：
2018-04
影响因子：
3.8
通讯作者：
Horn M
中科院分区：
文献类型：
--
作者：
Leontovyč A;Ulrychová L;O'Donoghue AJ;Vondrášek J;Marešová L;Hubálek M;Fajtová P;Chanová M;Jiang Z;Craik CS;Caffrey CR;Mareš M;Dvořák J;Horn M
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. 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. 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. Schistosomiasis (bilharziasis) is a global parasitic infection with more than 240 million people infected. It is caused by Schistosoma flatworms that live in the bloodstream. Current treatment relies on one drug, and no effective vaccine has yet been developed. Proteolytic enzymes (proteases) help the parasite survive in the mammalian host, allowing the schistosome to invade, feed, grow, reproduce and, manipulate the immune system. Thus, proteases are considered potential drug and vaccine targets. We previously described, and herein, investigate at the protein level, SmSP2, the major serine protease produced by the blood-dwelling stages of S. mansoni. We show that SmSP2 is secreted by the parasite and effectively processes host blood bioactive peptides and proteins that are involved in fibrinolysis and regulation of vascular tone. We propose, therefore, that SmSP2 modulates host hemostasis to promote parasite infection and survival. Thus, SmSP2 and similar proteins in other parasitic flatworms represent potential targets for novel drug or vaccine interventions.
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影响因子：
3.8
作者：
Dvorák J;Mashiyama ST;Sajid M;Braschi S;Delcroix M;Schneider EL;McKerrow WH;Bahgat M;Hansell E;Babbitt PC;Craik CS;McKerrow JH;Caffrey CR
通讯作者：
Caffrey CR
影响因子：
15.8
作者：
Abdulla MH;Lim KC;Sajid M;McKerrow JH;Caffrey CR
通讯作者：
Caffrey CR
影响因子：
--
作者：
Dolecková-Maresová, L;Pavlík, M;Mares, M
通讯作者：
Mares, M
影响因子：
4
作者：
Dvorak, Jan;Horn, Martin
通讯作者：
Horn, Martin
DOI：
10.1016/b978-0-12-382219-2.00575-5
发表时间：
2013-01-01
期刊：
HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION
影响因子：
--
作者：
Baird, Teaster T., Jr.;Craik, Charles S.
通讯作者：
Craik, Charles S.