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

Autor: Elzoheiry M; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA; Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Egypt., Da'dara AA; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA., Nation CS; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA., El-Beshbishi SN; Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Egypt., Skelly PJ; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. Electronic address: Patrick.Skelly@Tufts.edu.
Jazyk: angličtina
Zdroj: Molecular and biochemical parasitology [Mol Biochem Parasitol] 2019 Sep; Vol. 232, pp. 111190. Date of Electronic Publication: 2019 May 30.
DOI: 10.1016/j.molbiopara.2019.111190
Abstrakt: 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 K m 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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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