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Schistosomes can hydrolyze proinflammatory and prothrombotic polyphosphate (polyP) via tegumental alkaline phosphatase, SmAP

Author:
Elzoheiry, Manal, Da’dara, Akram A., Nation, Catherine S., El-Beshbishi, Samar N., Skelly, Patrick J.
Source:
Molecular and biochemical parasitology 2019 v.232 pp. 111190
ISSN:
0166-6851
Subject:
RNA interference, Schistosoma mansoni, adults, alkaline phosphatase, blood flow, blood platelets, females, genes, habitats, humans, males, metabolites, parasites, pathogens, phosphates, polymers, proteins, schistosomiasis, schistosomula
Abstract:
Schistosoma mansoni is a long-lived intravascular trematode parasite that can infect humans causing the chronic debilitating disease, schistosomiasis. We hypothesize that the action of host-interactive proteins found at the schistosome surface allows the worms to maintain a safe, anti-thrombotic and anti-inflammatory environment around them in the bloodstream. One such protein is the ˜60 kDa alkaline phosphatase SmAP which is known to be expressed in the outer tegument of all intravascular life stages. We demonstrate in this work that the parasites (schistosomula as well as adult males and females) can hydrolyze polyphosphate (polyP) - an anionic, linear polymer of inorganic phosphates that is produced and released by immune cells as well as by activated platelets and that induce proinflammatory and prothrombotic pathways. Purified recombinant SmAP can likewise cleave polyP and with a Km of 6.9 ± 1 mM. Finally, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to hydrolyze polyP. SmAP-mediated cleavage of polyP may contribute to the armamentarium of schistosomes that promotes their survival in the hostile intravascular habitat. This is the first report of any pathogen cleaving this bioactive metabolite.
Agid:
6461387