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GLYCOLYTIC ENZYMES AS VACCINES AGAINST SCHISTOSOMIASIS: TESTING SCHISTOSOMA MANSONI PHOSPHOGLYCERATE MUTASE IN MICE
Journal of Parasitology ( IF 1.3 ) Pub Date : 2024-03-11 , DOI: 10.1645/23-7
David B. Pirovich 1 , Akram A. Da'dara 1 , Patrick J. Skelly 1
Affiliation  

Schistosomiasis is a globally burdensome parasitic disease caused by flatworms (blood flukes) in the genus Schistosoma. The current standard treatment for schistosomiasis is the drug praziquantel, but there is an urgent need to advance novel interventions such as vaccines. Several glycolytic enzymes have been evaluated as vaccine targets for schistosomiasis, and data from these studies are reviewed here. Although these parasites are canonically considered to be intracellular, proteomic analysis has revealed that many schistosome glycolytic enzymes are additionally found at the host-interactive surface. We have recently found that the intravascular stage of Schistosoma mansoni (Sm) expresses the glycolytic enzyme phosphoglycerate mutase (PGM) on the tegumental surface. Live parasites display PGM activity, and suppression of PGM gene expression by RNA interference diminishes surface enzyme activity. Recombinant SmPGM (rSmPGM) can cleave its glycolytic substrate, 3-phosphoglycerate and can both bind to plasminogen and promote its conversion to an active form (plasmin) in vitro, suggesting a moonlighting role for this enzyme in regulating thrombosis in vivo. We found that antibodies in sera from chronically infected mice recognize rSmPGM. We also tested the protective efficacy of rSmPGM as a vaccine in the murine model. Although immunization generates high titers of anti-SmPGM antibodies (against both recombinant and native SmPGM), no significant differences in worm numbers were found between vaccinated and control animals.



中文翻译:

糖酵解酶作为血吸虫病疫苗:在小鼠中测试曼索尼血吸虫磷酸甘油酸变位酶

血吸虫病是一种全球性的寄生虫病,由血吸虫属扁虫(血吸虫)引起。目前血吸虫病的标准治疗方法是药物吡喹酮,但迫切需要推进疫苗等新型干预措施。几种糖酵解酶已​​被评估为血吸虫病疫苗靶标,本文综述了这些研究的数据。尽管这些寄生虫通常被认为是细胞内的,但蛋白质组学分析表明,在宿主相互作用的表面还发现了许多血吸虫糖酵解酶。我们最近发现曼氏血吸虫(Sm)的血管内阶段在皮膜表面表达糖酵解酶磷酸甘油酸变位酶(PGM)。活寄生虫表现出 PGM 活性,通过 RNA 干扰抑制 PGM 基因表达会降低表面酶活性。重组 SmPGM (rSmPGM) 可以裂解其糖酵解底物 3-磷酸甘油酸,并且可以与纤溶酶原结合并促进其在体外转化为活性形式(纤溶酶),这表明该酶在调节体内血栓形成中发挥兼职作用。我们发现慢性感染小鼠血清中的抗体可识别 rSmPGM。我们还在小鼠模型中测试了 rSmPGM 作为疫苗的保护功效。尽管免疫产生高滴度的抗 SmPGM 抗体(针对重组和天然 SmPGM),但在接种疫苗的动物和对照动物之间未发现蠕虫数量存在显着差异。

更新日期:2024-03-15
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