title: Biochemical and biophysical methodologies open the road for effective schistosomiasis therapy and vaccination.
abstract: Schistosomiasis caused by blood-dwelling flukes, namely Schistosoma mansoni and Schistosoma haematobium is a severe debilitating disease, widespread in sub-Saharan Africa, the Middle East, and South America. Developing and adult worms are unscathed by the surrounding immune effectors and antibodies because the parasite is protected by a double lipid bilayer armor which allows access of nutrients, while binding of specific antibodies is denied.
  
  
  
  Fluorescence recovery after bleaching, extraction of surface membrane cholesterol by methyl-β-cyclodextrin, inhibition and activation of sphingomyelin biosynthesis and hydrolysis, and elastic incoherent and quasi-elastic neutron scattering approaches have helped to clarify the basic mechanism of this immune evasion, and showed that sphingomyelin (SM) molecules in the worm apical lipid bilayer form with surrounding water molecules a tight hydrogen bond barrier. Viability of the parasite and permeability of the outer shield are controlled by equilibrium between SM biosynthesis and activity of a tegument-associated neutral sphingomyelinase (nSMase).
  
  
  
  Excessive nSMase activation by polyunsaturated fatty acids (PUFA), such as arachidonic acid (ARA) leads to disruption of the SM molecules and associated hydrogen bond network, with subsequent access of host antibodies and immune effectors to the outer membrane and eventual parasite death.
  
  
  
  ARA was predicted and shown to be a potent schistosomicide in vitro and in vivo in experimental animals and in children. Additionally, it was advocated that schistosomiasis vaccine candidates should be selected uniquely among excretory-secretory products of developing worms, as contrary to cytosolic and surface membrane antigens, they are able to activate the effector functions of the host antibodies and toxic molecules. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo".
authors.affiliation: Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt. Electronic address: rashikaelridi@hotmail.com.
authors.forename: Rashika
authors.initials: R
authors.lastname: El Ridi
authors.affiliation: Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt; Department of Chemistry, School of Science and Engineering, American University in Cairo, New Cairo, 11835 Cairo, Egypt.
authors.forename: Hatem
authors.initials: H
authors.lastname: Tallima
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Migliardo
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods*; D001703:Biophysics / Q000379:methods*; D057131:Immune Evasion; D012547:Schistosoma / Q000254:growth & development / Q000276:immunology; D012552:Schistosomiasis / Q000276:immunology* / Q000628:therapy*; D014611:Vaccination
keywords: Arachidonic acid; Elastic incoherent and quasi-elastic neutron scattering; Hydrogen bond barrier; Neutral sphingomyelinase; Schistosoma; Sphingomyelin