title: Haem uptake is essential for egg production in the haematophagous blood fluke of humans, Schistosoma mansoni.
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.
authors.affiliation: School of Veterinary Sciences, The University of Queensland, Gatton, Queensland, Australia.|QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Shu Qin
authors.initials: SQ
authors.lastname: Toh
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Malagón Martínez
authors.affiliation: School of Veterinary Sciences, The University of Queensland, Gatton, Queensland, Australia.|QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D005816:Genetic Complementation Test; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008652:Mesoporphyrins / Q000378:metabolism; D008969:Molecular Sequence Data; D009866:Oogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D010165:Palladium / Q000378:metabolism; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012550:Schistosoma mansoni / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D005456:Fluorescent Dyes; D015801:Helminth Proteins; D026901:Membrane Transport Proteins; D008652:Mesoporphyrins; D006418:Heme; C031468:mesoporphyrin IX; D010165:Palladium; D016572:Cyclosporine
keywords: Schistosoma mansoni; fecundity; haem uptake; haem-responsive gene; parasite