Research Article: Magnetic Beads for Schistosomiasis Diagnosis

Date Published: December 26, 2007

Publisher: Public Library of Science

Author(s): Malcolm K. Jones, Julie Balen, Jeffrey Bethony

Abstract: None

Partial Text: Schistosomiasis is a chronic helminth disease of humans, linked persistently with poverty. Parasite transmission is reliant on poor sanitation for transmission from humans to the molluscan intermediate host [1],[2]. Recent estimates of the global disease burden for schistosomiasis indicate that some 207 million people are infected, with over 750 million people at risk [2]. New control strategies include evidence-based approaches, which incorporate targeted chemotherapy in areas of low endemicity (≤10% prevalence) and mass drug administration in regions of moderate to high endemicity [1]. The changing landscape of schistosomiasis burdens brought about by such strategies [1], the altered geographical distribution of the parasites arising from changes to irrigation patterns and consequent effects on snail host distribution [2], and the looming spectre of resistance to the primary drug, praziquantel, emphasise the immediate need for highly specific and sensitive parasite surveillance methodology to be deployed [3].

A recent article by Fagundes Teixeira and colleagues [5] in this journal describes the intriguing discovery that paramagnetic beads, under the influence of a magnetic field, can be used to partially purify S. mansoni eggs from faeces for subsequent morphological identification. The original premise of the work was that eggs could be purified from faecal samples in solution by biotinylated lectins and streptavidin-conjugated beads. Lectins were theorised to bind carbohydrate moieties on eggshells and, using the strong affinity of streptavidin for biotin, egg-paramagnetic bead complexes could be entrapped in a magnetic field for subsequent purification. The authors were able to purify eggs, but not in the manner they had hypothesised, for it turned out that the beads themselves, not the lectin intermediates, were binding the schistosome eggs. With further exploration, they showed that antibody-conjugated beads could also bind eggs, although with less efficiency. Latex beads conjugated to protein-A did not allow for egg purification. From these results, the authors argued that the beads themselves, under the influence of an external magnetic field, could bind the eggs.

How can this affinity of the paramagnetic beads for schistosome eggs be explained? A possible answer comes from recent studies of iron (Fe) metabolism of schistosomes [6]. Earlier work had shown that female schistosomes accumulate iron in vitellocytes, cells of the female germinal line that synthesise eggshell precursors [7],[8]. The role of Fe in early development of schistosomes, however, remained uncertain. Energy dispersive spectroscopy of S. japonicum eggshells demonstrated that Fe is incorporated into the eggshell [6]. Schistosome eggshells are quinone-tanned, a chemical process in which eggshell precursors are modified under the action of tyrosinase enzymes [9]. Tyrosinases catalyse both the hydroxylation of tyrosine residues in eggshell precursor proteins to dihydroxy-phenylalanine and the subsequent oxidation to dopaquinone. In other invertebrates, the cross-linking reaction appears to be highly dependent on Fe, which acts to stabilise and strengthen the bridge (see [6]). The hypothesis, then, is that vitellocyte Fe is used by female worms in eggshell stabilisation. The explanation for the affinity of the paramagnetic beads and schistosome eggs is that it is the presence of Fe in eggshells that allows the affinity of the beads for eggshells in the presence of an external magnetic field. Under action of such a field, the paramagnetic beads themselves become magnetic, enabling them to interact with the eggs.

The paper by Fagundes Teixeira et al. [5] raises two interesting concepts for schistosomiasis studies. Firstly, the work reminds us that there are many fundamental questions to be answered with regard to the structural biology and chemistry of egg formation in schistosomes. Schistosome eggs have been largely refractory to structural analyses because they are resistant to hydrolysis by enzymes and because they appear to be synthesised from multiple precursor proteins [10]. Further studies of the structural biology of eggshells are of great importance because of the central role that eggs play in the schistosome–human host interplay and resultant morbidity.

Source:

http://doi.org/10.1371/journal.pntd.0000159

 

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