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Schistosomes can hydrolyze proinflammatory and prothrombotic polyphosphate (polyP) via tegumental alkaline phosphatase, SmAP.
Molecular and Biochemical Parasitology ( IF 1.4 ) Pub Date : 2019-05-30 , DOI: 10.1016/j.molbiopara.2019.111190
Manal Elzoheiry 1 , Akram A Da'dara 2 , Catherine S Nation 2 , Samar N El-Beshbishi 3 , Patrick J Skelly 2
Affiliation  

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.



中文翻译:


血吸虫可以通过皮膜碱性磷酸酶 SmAP 水解促炎和促血栓形成的多磷酸盐 (polyP)。



曼氏血吸虫是一种长寿的血管内吸虫寄生虫,可以感染人类,导致慢性衰弱性疾病——血吸虫病。我们假设血吸虫表面发现的宿主相互作用蛋白的作用使线虫能够在血液中维持其周围安全、抗血栓和抗炎的环境。一种这样的蛋白质是~60kDa碱性磷酸酶SmAP,已知其在所有血管内生命阶段的外皮中表达。我们在这项工作中证明,寄生虫(血吸虫以及成年男性和女性)可以水解聚磷酸盐(polyP)——一种无机磷酸盐的阴离子线性聚合物,由免疫细胞以及活化的血小板产生和释放,并诱导促炎和促血栓途径。纯化的重组 SmAP 同样可以裂解 polyP,K m为 6.9 ± 1 mM。最后,SmAP基因被RNAi抑制的寄生虫水解polyP的能力显着受损。 SmAP 介导的 PolyP 裂解可能有助于血吸虫的装备,促进其在敌对的血管内栖息地中生存。这是任何病原体裂解这种生物活性代谢物的第一份报告。

更新日期:2019-05-30
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