ABSTRACT
Schistosomes ingest host erythrocytes, liberating large quantities of haem. Despite its toxicity, haem is an essential factor for numerous biological reactions, and may be an important iron source for these helminths. We used a fluorescence haem analogue, palladium mesoporphyrin, to investigate pathways of haem acquisition, and showed that palladium mesoporphyrin accumulates in the vitellaria (eggshell precursor glands) and ovary of female Schistosoma mansoni. Furthermore, incubation of adult females in 10-100 µm cyclosporin A (IC50 = 2.3 µm) inhibits the uptake of palladium mesoporphyrin to these tissues, with tenfold reductions in fluorescence intensity of the ovary. In vitro exposure to cyclosporin A resulted in significant perturbation of egg production, reducing egg output from 34 eggs per female to 5.7 eggs per female over the incubation period, and retardation of egg development. We characterized a S. mansoni homologue of the haem-responsive genes of Caenorhabditis elegans. The gene (Smhrg-1) encodes a protein with a molecular weight of approximately 17 kDa. SmHRG-1 was able to rescue growth in haem transport-deficient HEM1Δ yeast. Transcriptional suppression of Smhrg-1 in adult S. mansoni worms resulted in significant delay in egg maturation, with 47% of eggs from transcriptionally suppressed worms being identified as immature compared with only 27% of eggs laid by control worms treated with firefly luciferase. Our findings indicate the presence of transmembrane haem transporters in schistosomes, with a high abundance of these molecules being present in tissues involved in oogenesis.
Subject(s)
Heme/metabolism , Oogenesis/physiology , Schistosoma mansoni/metabolism , Amino Acid Sequence , Animals , Biological Transport, Active/genetics , Cyclosporine/pharmacology , Female , Fluorescent Dyes/metabolism , Gene Knockdown Techniques , Genes, Helminth , Genetic Complementation Test , Helminth Proteins/chemistry , Helminth Proteins/genetics , Helminth Proteins/metabolism , Humans , Membrane Transport Proteins/chemistry , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Mesoporphyrins/metabolism , Molecular Sequence Data , Oogenesis/drug effects , Oogenesis/genetics , Palladium/metabolism , Phylogeny , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Schistosoma mansoni/genetics , Schistosoma mansoni/growth & development , Sequence Homology, Amino AcidABSTRACT
Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification.
