Fluorescent lipid uptake and transport in adult Schistosoma mansoni

Parasitology ◽  
1992 ◽  
Vol 105 (1) ◽  
pp. 81-89 ◽  
Author(s):  
D. Moffat ◽  
J. R. Kusel
Keyword(s):  
Schistosoma Mansoni ◽  
External Medium ◽  
Surface Membrane ◽  
Lipid Uptake ◽  
Lipophilic Compounds ◽  
Oesophageal Gland ◽  
Labelled Compound ◽  
Positively Charged ◽  
Uptake And Transport

Fluorescent lipophilic compounds can be used to label the surface membrane of Schistosoma mansoni by adding the compound in small amounts of organic solvents to aqueous medium in vitro. Under these conditions it is difficult to follow routes of distribution of the label. Here we have absorbed nitrobenzoxadiazolamine methylamino–(NBD)–ceramides to positively charged Dowex beads, and incubated the labelled beads with living parasites. The NBD–ceramide transfers to the surface membrane as a patch 50–100 μm in diameter, after which the label can be seen localized in the gut and in a very concentrated form in organelles within the oesophageal gland cells. Subsequently the labelled compound can be found in organelles within other body cells, including subtegumental cells. We show that the labelled ceramide has been transported from the patch in the surface membrane through internal membrane systems to the destination in the gut and oesophageal gland and not transported through the gut via the external medium. A different pattern was observed when NBD–cholesterol was used. The pharynx was rapidly labelled when NBD–cholesterol was added in medium with or without serum or attached to red blood cells only. Diffuse labelling of the surface membrane and oesophageal gland occurred. We have demonstrated a novel route of lipid transport within the parasite. The route requires the surface membrane to have very specialized regions to facilitate such transport.

Schistosoma mansoni: a comparative study of artificially transformed schistosomula and schistomula recoverd after cercarial penetration of isolated skin

Parasitology ◽  
1977 ◽  
Vol 74 (1) ◽  
pp. 73-86 ◽  
Author(s):  
Linda H. Brink ◽  
Diane J. McLaren ◽  
S. R. Smithers
Keyword(s):  
Comparative Study ◽  
Schistosoma Mansoni ◽  
Amorphous Material ◽  
Surface Membrane ◽  
Antigenic Determinants ◽  
Agglutination Reaction ◽  
Rat Serum ◽  
Mechanical Separation ◽  
B Blood Group

A comparison was made of the ultrastructure, development and antigenic nature of the surfaces and of the viability of three types of schistosomula of Schistosoma mansoni: schistosomula formed afrer cercariae had penetrated isolated skin (SS), schistosomula produced after mechanical separation of cercarial tails from bodies (MS), and schistosomula transformed from cercariae after incubation in fresh rat serum (RS).Within 2 h of transformation, the surface membrane of all three types of schistosomula had changed from trilaminate to heptalaminate structures and SS and MS had lost their cercarial glycocalyx. Initially a dense amorphous material was demonstrated on the surfaces of RS, which was thought to be the result of an interaction between a factor in rat serum and the glycocalyx: this material was greatly reduced within 2 h of transformation. The pre-acetabular glands of SS were emptied while those of MS and RS retained their contents. Immunofluorescent studies showed that all schistosomula bound serum from mice immune to S. mansoni, but the binding was stronger with MS and RS. The mixed agglutination reaction demonstrated the presence of human A and B blood group-like antigenic determinants on approximately 30% of 3 h old SS; these determinants were not detected on MS or RS. In vitro, the development of MS and RS was similar to SS; the first schistosomula reached the ‘gut-closed’ stage by day 10; 50–70% of SS reached this stage by day 12, in contrast to only 25–50% of MS and RS. Between 28 and 45% of all schistosomula developed to maturity when injected intravenously into mice.It was concluded that the two types of artificially prepared schistosomula fultil the main criteria of transformation from cercaria to schistosomulum. Further, it is suggested that MS are the most appropriate source of material for immunochemical and physiological studies.

The use of membrane-active compounds to examine the structure of the surface membrane of Schistosoma mansoni

1981 ◽  
Vol 1 (3) ◽  
pp. 253-261 ◽  
Author(s):  
J. R. Kusel ◽  
L. Stones ◽  
W. Harnett
Keyword(s):  
Schistosoma Mansoni ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Surface Membrane ◽  
Lipid Phase ◽  
Active Compounds ◽  
Lipophilic Compounds ◽  
Young Stage

The effects of. a variety of lipophilic compounds on the young stage (schistosomulum) and adult Schistosoma mansoni have been studied by measuring the release of51Cr and125I-labelled wheat-germ agglutinin from labelled parasites. The compounds could be classified into three groups, one of which described reagents which affected only the schistosomulum. It is concluded that during development, changes occur in the organization of the lipid phase of the parasite membrane

Damage to surface membrane ofSchistosoma mansoniby pristane (2,6,10,14 tetramethyl pentadecane) and other hydrophobic compounds

Parasitology ◽  
1980 ◽  
Vol 80 (1) ◽  
pp. 83-94 ◽  
Author(s):  
J. R. Kusel ◽  
L. Stones ◽  
L. Tetley
Keyword(s):  
Schistosoma Mansoni ◽  
Organic Solvents ◽  
Intraperitoneal Injection ◽  
Trypan Blue ◽  
Surface Membrane ◽  
Hydrophobic Compounds ◽  
Release Studies ◽  
Significant Release

SummaryIntraperitoneal injection of cercariae into pristane (2, 6, 10, 14 tetramethyl pentadecane)-primed Balb/c mice led to greatly diminished numbers of portal and peritoneal worms compared with untreated mice. Schistosomula taken from the peritoneal cavity of pristane-primed mice carried globules of pristane on their surfaces, were contracted and were permeable to Trypan blue. Pristane globules bound also to adult wormsin vitroandin vivocausing rapid damage to the surface membrane. Hydrophobic compounds other than hydrocarbons either bound without causing gross damage, or did not bind to the adult worms.51Cr release studies showed that pristane had no effect on the permeability of human erythrocytes, while causing significant release from both schistosomula and adult worms. The binding of hydrocarbon globules to a variety of other parasites did not occur. The binding ofn-[1-14C]hexadecane to adultSchistosoma mansoniwas significantly decreased by extraction of the parasite with organic solvents or treatment with staphylococcal δ toxin, which interacts with phospholipids in the membrane. Possible mechanisms of damage of the parasite by the hydrocarbons are discussed.

Acquisition of host antigens by young Schistosoma mansoni in mice: correlation with failure to bind antibody in vitro

Parasitology ◽  
1975 ◽  
Vol 70 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Diane J. McLaren ◽  
J. A. Clegg ◽  
S. R. Smithers
Keyword(s):  
Horseradish Peroxidase ◽  
Rhesus Monkey ◽  
Schistosoma Mansoni ◽  
Surface Membrane ◽  
Mouse Skin ◽  
Ultrastructural Level ◽  
High Titre ◽  
Immune Serum ◽  
Mouse Erythrocyte

Young schistosomes collected after penetration through isolated mouse skin (3 h schistosomula) were cultured in medium containing immune rhesus monkey serum with a high titre of antibody known to kill schistosomula in the presence of complement. Morphological signs of damage in electron micrographs were confined to the surface tegument of the schistosomula. Antibodies in immune rhesus serum were shown to bind to the surface membrane of 3 h schistosomula using an antibody-enzyme bridge technique involving labelling with horseradish peroxidase and histochemical localization of the enzyme at the ultrastructural level. Schistosomula recovered from the lungs of mice 4 days after infection did not bind monkey antibodies at the surface and these 4-day schistosomula are not susceptible to damage by immune serum in vitro. Mouse erythrocyte antigens were detected on the surface of 4-day schistosomula using an appropriate antibody-enzyme bridge but these host antigens could not be found on 3 h schistosomula. This correlation between the presence of mouse host antigens on the surface of schistosomula and the inability of immune monkey antibodies to bind to the surface membrane is consistent with the hypothesis that host antigens are acquired by young schistosomes and serve to protect the surface membrane against antibody-mediated damage.

scholarly journals In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium

2010 ◽  
Vol 54 (8) ◽  
pp. 3383-3389 ◽  
Author(s):  
Rashika El Ridi ◽  
Marwa Aboueldahab ◽  
Hatem Tallima ◽  
Mohamed Salah ◽  
Noha Mahana ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Schistosoma Mansoni ◽  
Schistosoma Haematobium ◽  
Unsaturated Fatty Acids ◽  
Ex Vivo ◽  
Surface Membrane ◽  
Calf Serum ◽  
The United States

ABSTRACT The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old Schistosoma mansoni and 9-, 10-, and 12-week-old Schistosoma haematobium worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl2 and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated S. mansoni and S. haematobium worm attrition was reproduced in vivo in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy.

scholarly journals Loss of covalently labeled glycoproteins and glycolipids from the surface of newly transformed schistosomula of Schistosoma mansoni.

1982 ◽  
Vol 94 (2) ◽  
pp. 363-369 ◽  
Author(s):  
J C Samuelson ◽  
J P Caulfield
Keyword(s):  
Schistosoma Mansoni ◽  
Trichloroacetic Acid ◽  
Culture Medium ◽  
Surface Membrane ◽  
Apparent Molecular Weight ◽  
Acid Precipitation ◽  
Defined Medium ◽  
Galactose Oxidase ◽  
Newly Transformed Schistosomula

Schistosomula of Schistosoma mansoni were labeled by oxidation with galactose oxidase or with periodate followed by reduction with NaB3H4 to study the loss of the surface membrane of these parasites in vitro. Grain counts of light microscope autoradiographs (LMARG) of radiolabeled schistosomula show that both galactose oxidase and periodate specifically label the surface of the organisms. Galactose oxidase labels 11 glycoproteins on the surface of skin and mechanical schistosomula, ranging in apparent molecular weight from 17,000 to greater than 105,000. These glycoproteins are lost from the surface of schistosomula with a halftime of 10-15 h in culture in defined medium. Most of these glycoproteins appear to be shed intact from the surface of the schistosomula rather than endocytosed and degraded, because greater than 50% of each of the lost proteins can be recovered by trichloroacetic acid precipitation of the culture medium and because there is no internalization of the radiolabels into cultured schistosomula examined by LMARG. In addition to glycoproteins, periodate labels at least seven glycolipids on the surface of mechanical schistosomula. After culture for 15 h, more than half of each of these periodate-labeled proteins and lipids are lost from the schistosomula, and their abundance relative to each other remains similar to that of freshly labeled organisms. Since both proteins and lipids are lost from the surface of the schistosomula at the same rate, we believe that we are observing a general loss of the parasite surface membrane.

In vitro schistosomicidal activity of Usnea steineri extract and its major constituent (+)-usnic acid against Schistosoma mansoni

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
AIO Salloum ◽  
R Lucarini ◽  
MG Tozatti ◽  
J Medeiros ◽  
MLA Silva ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Usnic Acid ◽  
Major Constituent

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

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