Tracking the fate of iron in early development of human blood flukes

Abstract

Iron (Fe) is an important trace element found in nearly all organisms, and is used as a cofactor in many biological reactions. One role for Fe in some invertebrates is in stabilization of extracellular matrices. The human blood fluke, Schistosoma japonicum, is responsible for significant human disease in developing and tropical nations. Disease in humans arises from host immunological reaction to parasite eggs that lodge in tissues. Schistosomes require Fe for development in their hosts, and store abundant Fe in vitelline (eggshell-forming) cells of the female system. The understanding of Fe metabolism and functionality are aspects of its biology that may be exploited in future therapeutics. The biology of Fe stores in vitelline cells of S. japonicum was investigated to illuminate possible functions of this element in early development of these parasites. Vitelline Fe is stored in yolk ferritin that is upregulated in females and is also expressed at low levels in egg-stages and adult males. Laser microdissection microscopy, coupled with reverse transcriptase- and real time-PCR amplification of schistosome ferritin sequences, confirmed that the vitelline cells are the likely progenitor cells of yolk ferritin. Assessment of Fe concentrations in whole male and whole female adult worms, eggs and purified eggshells by colorimetric assays and mass spectroscopy demonstrated higher levels of Fe in the female parasite, but also high levels of the element in whole parasite eggs and purified eggshell. Qualitative energy dispersive spectroscopy of purified eggshells, revealed that Fe is abundant in the eggshell, the matrix of which is composed of heavily cross-linked eggshell precursor proteins. Thus, vitelline stores of Fe are implicated in eggshell cross-linking in platyhelminths. These observations emphasise the importance of Fe in schistosome metabolism and egg formation and suggest new avenues for disruption of egg formation in these pathogenic parasites.

Differences in genomic architecture between two distinct geographical strains of the blood fluke Schistosoma japonicum reveal potential phenotype basis

“…Regulation and utilisation of iron is a critical co-factor in schistosome biology with strong indications that it plays a major role in the fecundity of adult female parasites [62]. One of these genes with a potential role in iron metabolism identified in this study encodes a probable transferrin-binding protein 1 homologue (Contig 03542), localised to a sub-genomic region in SjC.…”

Urinary schistosomiasis

“…Of these symptoms, terminal hematuria may be the most feasible and is often the basis for epidemiologic diagnosis. Iron deficiency anemia may be exacerbated by co-morbidity with other endemic tropical [14]. In addition, host iron recycling is disrupted by a pro-inflammatory synthesis of hepcidin, an acute phase reactant [15].…”

Thioredoxin Glutathione Reductase-Dependent Redox Networks in Platyhelminth Parasites

“…Therefore, sequestration of metal ions under conditions of stress is an important antioxidant defense strategy. In mammals, among other proteins, ferritins (an ''iron cage'') and metallothioneins (Cys-rich proteins that chelate copper and heavy metals) are (16,28), but metallothioneins have not been described (and their identification by similarity is not trivial). Interestingly, it has recently been proposed that copper and heavy metal sequestration in platyhelminth parasites probably relies on phytochelatins, Cys-rich oligopeptides with the basic structure of (c-GluCys) n Gly, with n = 2-11 (43).…”