The human blood parasite Schistosoma mansoni expresses extracellular tegumental calpains that cleave the blood clotting protein fibronectin

Schistosomes are intravascular, parasitic flatworms that cause debilitating disease afflicting >200 million people. Proteins expressed at the host-parasite interface likely play key roles in modifying the worm's local environment to ensure parasite survival. Proteomic analysis reveals that two proteases belonging to the calpain family (SmCalp1 and SmCalp2) are expressed in the Schistosoma mansoni tegument. We have cloned both; while highly conserved in domain organization they display just 31% amino acid sequence identity. Both display high relative expression in the parasite's intravascular life forms. Immunolocalization and activity based protein profiling experiments confirm the presence of the enzymes at the host-parasite interface. Living parasites exhibit surface calpain activity that is blocked in the absence of calcium and in the presence of calpain inhibitors (E64c, PD 150606 and calpastatin). While calpains are invariably reported to be exclusively intracellular (except in diseased or injured tissues), our data show that schistosomes display unique, constitutive, functional extracellular calpain activity. Furthermore we show that the worms are capable of cleaving the host blood clotting protein fibronectin and that this activity can be inhibited by E64c. We hypothesize that SmCalp1 and/or SmCalp2 perform this cleavage function to impede blood clot formation around the worms in vivo.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:7

Enthalten in:

Scientific reports - 7(2017), 1 vom: 10. Okt., Seite 12912

Sprache:

Englisch

Beteiligte Personen:

Wang, Qiang [VerfasserIn]
Da'dara, Akram A [VerfasserIn]
Skelly, Patrick J [VerfasserIn]

Links:

Volltext

Themen:

Blood Proteins
Calpain
EC 3.4.22.-
Fibronectins
Journal Article
Research Support, N.I.H., Extramural

Anmerkungen:

Date Completed 27.06.2019

Date Revised 09.08.2023

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-017-13141-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM276872967