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The Essential Ectoenzyme SmNPP5 from the Human Intravascular Parasite Schistosoma mansoni is an ADPase and a Potent Inhibitor of Platelet Aggregation
Open accessAbstract
Schistosomes are intravascular parasitic platyhelminthes infecting > 200 million people globally and causing a debilitating disease, schistosomiasis. Despite the relatively large size of the adult worms and their disruption of blood flow, surprisingly, they do not appear to provoke thrombus formation around them in vivo. We hypothesize that proteins expressed at the host–parasite interface are key to this ability. Here, we functionally express an ectonucleotide pyrophosphatase/phosphodiesterase homologue, SmNPP5, that is expressed at the tegumental surface of intravascular Schistosoma mansoni. We report that SmNPP5, a known virulence factor for the worms, is a type one glycoprotein that cleaves the artificial substrate p-Nph-5′-TMP in a reaction that requires cations and at an optimal pH of 9. Using immunolocalization and enzyme activity measurements, we confirm that SmNPP5 is exclusively expressed at the host interactive surface of all intravascular life stages. SmNPP5 inhibits platelet aggregation in a dose-dependent manner, as measured by multiple electrode aggregometry (MEA) using whole blood. Inhibition is apparent when either collagen or adenosine diphosphate (ADP) is used as agonist but is lost following heat treatment of SmNPP5. Unlike its mammalian homologue, NPP5, the schistosome protein cleaves ADP and with a Km of 246 ± 34 µM. In sum, SmNPP5 is expressed in the intravascular environment where it can degrade ADP and act as an anticoagulant. In this manner, the protein likely helps limit blood clot formation around the worms in vivo to permit the parasites free movement within the vasculature.
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“Schistosome teguments contain ATP diphosphohydrolase (SmATPDase1) (Da’dara et al., 2014) and the ectonucleotide pyrophosphatase/phosphodiesterase homolog SmNPP5 (Elzoheiry et al., 2018), both of which degrade ATP and ADP to non-thrombotic AMP.”
From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Elzoheiry et al., 2018
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Sorted by citations
Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules
Maizels, R. M., Smits, H. H., & McSorley, H. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.10.016 · Cited by 435
Metadata
- Authors
- Elzoheiry, M., Da'dara, A., deLaforcade, A., El-Beshbishi, S., & Skelly, P.
- Affiliations
- Tufts University (US)
- Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States
- Mansoura University (EG)
- Corresponding author
- Skelly, Patrick
- Venue
- Thrombosis and Haemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2018-04-18
- Volume
- 118
- Issue
- 06
- Pages
- 979-989
- ISSN
- 0340-6245 (ISSN-L)
- 2567-689X
- PMC
- PMC12434806
- OpenAlex
- W2802310778
- Cited by
- 28
- References
- 35
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 2
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R56AI056273, R01AI056273)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- Schistosoma mansoni, ectoenzymes, ADPase, platelet aggregation inhibition, anticoagulants, schistosomiasis, host-parasite interface, tegument, virulence factors, adenosine diphosphate, collagen-induced aggregation, host-parasite interactions
- MeSH terms
- Adenosine Diphosphate, Animals, Apyrase, Blood Platelets, Blood Vessels, Female, Humans, Male, Phosphoric Diester Hydrolases, Platelet Aggregation Inhibitors, Pyrophosphatases, Schistosoma mansoni, Schistosomiasis mansoni, Helminth Proteins, Virulence Factors, Mice
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