Search In this Thesis
   Search In this Thesis  
العنوان
Characterization of schistosome host-interactive tegumental proteins /
المؤلف
El-Zoheiry, Manal Ali Heidar Mohamed Ali Hassan.
هيئة الاعداد
باحث / منال على حيدر محمد على حسن الزهيرى
مشرف / السعيد ابراهيم الخولى
مشرف / سمر نجاح البشبيشى
مشرف / منار صبح عزب
مشرف / باتريك اسكيلى
مناقش / سلامه أحمد عبدالمجيد
مناقش / عزة إبراهيم يونس
الموضوع
Macromolecules. Schistosome. Tegumental Proteins.
تاريخ النشر
2018.
عدد الصفحات
125 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الطب (متفرقات)
تاريخ الإجازة
01/09/2018
مكان الإجازة
جامعة المنصورة - كلية الطب - Medical Parasitology
الفهرس
Only 14 pages are availabe for public view

from 144

from 144

Abstract

Schistosoma mansoni is a platyhelminth with expressed host-interactive proteins in the outer surface- tegument- that have been hypothesized to modulate the parasite local environment. Alkaline phosphatase (SmAP) is a tegumental ecto-nucleotidase that highly expressed in the intravascular stages, indicating its role in parasite accommodation in the hostile environment. Aim of the work : This study was conducted to express an active recombinant form of SmAP, in attempt to evaluate its role in parasite accommodation in the host blood through impact on pro-inflammatory and pro-thrombotic compounds. Illustrate the impact of recombinant tegumental phosphatases on platelet function using whole blood impedance, multiple electrode aggregometry (MEA). Method : SmAP was expressed in Chinese hamster ovary (CHO) cells, then used SDS/PAGE for identification, and colorimetric phosphate assay kit to show the dephosphorylation activity of rSmAP. The commercially synthetized siRNAs targeting SmAP was used to knockdown the gene expression and protein. Results : Purified recombinant SmAP is ~60 kDa, needs Mg+2 to be fully activated, and works maximally at pH of ~9. We show here that rSmAP can cleave adenosine monophosphate (AMP) to generate adenosine. In addition, we demonstrate that living schistosomes as well as rSmAP can break down other important host signalling molecules. These include sphingosine-1-phosphate (S1P), a sphingolipid that is a major regulator of the vascular and immune system. This is the first demonstration of any pathogen cleaving this key control molecule. Additionally, we show that live schistosomes as well as rSmAP can cleave polyphosphate (polyP), a potent, natural activator of the contact pathway of blood clotting. Conclusion : This work reveals that S. mansoni worms have the capability to impede host immune and haemostatic pathways by using a multifunctional tegumental SmAP to cleave important host signalling molecules in their vicinity.