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Metabolite movement across the schistosome surface

Published online by Cambridge University Press:  27 February 2012

A. Da'dara ,
G. Krautz-Peterson ,
Z. Faghiri  and
P.J. Skelly
A. Da'dara
Affiliation:
Molecular Helminthology Laboratory, Department of Biomedical Sciences, Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA
G. Krautz-Peterson
Affiliation:
Molecular Helminthology Laboratory, Department of Biomedical Sciences, Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA
Z. Faghiri
Affiliation:
Molecular Helminthology Laboratory, Department of Biomedical Sciences, Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA
P.J. Skelly*
Affiliation:
Molecular Helminthology Laboratory, Department of Biomedical Sciences, Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA
*
*E-mail: [email protected]
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Abstract

Intravascular schistosome parasites are covered by an unusual double lipid bilayer. Nutrients, such as glucose and amino acids, as well as other metabolites, are known to be transported across this surface via specific transporter proteins. For instance, the glucose transporter protein SGTP4 is found in the host-interactive tegumental membranes. A second glucose transporter, SGTP1, localizes to the tegumental basal membrane (and internal tissues). Following expression in Xenopus oocytes, SGTP1 and SGTP4 both function as facilitated-diffusion sugar transporters. Suppressing the expression of SGTP1 and SGTP4 in juvenile schistosomes using RNA interference (RNAi) impairs the parasite's ability to import glucose and severely decreases worm viability. Amino acids can also be imported into schistosomes across their surface and an amino acid transporter (SPRM1lc) has been localized in the parasite surface membranes (as well as internally). In Xenopus oocytes, SPRM1lc can import the basic amino acids arginine, lysine and histidine as well as leucine, phenylalanine, methionine and glutamine. To function, this protein requires the assistance of a heavy-chain partner (SPRM1hc) which acts as a chaperone. Water is transported across the tegument of schistosomes via the aquaporin protein SmAQP. Suppressing SmAQP gene expression makes the parasites less able to osmoregulate and decreases their viability. In addition, SmAQP-suppressed adult parasites have been shown to be impaired in their ability to excrete lactate. Analysis of tegumental transporter proteins, as described in this report, is designed to generate a comprehensive understanding of the role of such proteins in promoting parasite survival by controlling the movement of metabolites into and out of the worms.

Type
Research Papers
Information
Journal of Helminthology , Volume 86 , Issue 2 , June 2012 , pp. 141 - 147
Copyright
Copyright © Cambridge University Press 2012

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References

Asch, H.L. & Read, C.P. (1975a) Membrane transport in Schistosoma mansoni: transport of amino acids by adult males. Experimental Parasitology 38, 123–135.CrossRefGoogle ScholarPubMed
Asch, H.L. & Read, C.P. (1975b) Transtegumental absorption of amino acids by male Schistosoma mansoni. Journal of Parasitology 61, 378–379.CrossRefGoogle ScholarPubMed
Bhardwaj, R., Krautz-Peterson, G. & Skelly, P.J. (2011) Using RNA interference in Schistosoma mansoni. Methods in Molecular Biology 764, 223–239.CrossRefGoogle ScholarPubMed
Braschi, S. & Wilson, R.A. (2005) Proteins exposed at the adult schistosome surface revealed by biotinylation. Molecular & Cellular Proteomics 5, 347–356.CrossRefGoogle ScholarPubMed
Braschi, S., Curwen, R.S., Ashton, P.D., Verjovski-Almeida, S. & Wilson, R.A. (2006) The tegument surface membranes of the human blood parasite Schistosoma mansoni: a proteomic analysis after differential extraction. Proteomics 6, 1471–1482.CrossRefGoogle ScholarPubMed
Bueding, E. (1950) Carbohydrate metabolism of Schistosoma mansoni. Journal of General Physiology 33, 475–495.Google ScholarPubMed
Bueding, E. & Mansour, J.M. (1957) The relationship between inhibition of phosphofructokinase activity and the mode of action of trivalent organic antimonials on Schistosoma mansoni. British Journal of Pharmacology and Chemotherapy 12, 159–165.CrossRefGoogle ScholarPubMed
Castagna, M., Shayakul, C., Trotti, D., Sacchi, V.F., Harvey, W.R. & Hediger, M.A. (1997) Molecular characteristics of mammalian and insect amino acid transporters: implications for amino acid homeostasis. Journal of Experimental Biology 200, 269–286.CrossRefGoogle ScholarPubMed
Castro-Borges, W., Dowle, A., Curwen, R.S., Thomas-Oates, J. & Wilson, R.A. (2011a) Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: a rational approach to select vaccine candidates. PLoS Neglected Tropical Diseases 5, e993.CrossRefGoogle ScholarPubMed
Castro-Borges, W., Simpson, D.M., Dowle, A., Curwen, R.S., Thomas-Oates, J., Beynon, R.J. & Wilson, R.A. (2011b) Abundance of tegument surface proteins in the human blood fluke Schistosoma mansoni determined by QconCAT proteomics. Journal of Proteomics 74, 1519–1533.CrossRefGoogle ScholarPubMed
Chiang, C.P. & Caulfield, J.P. (1989) Human lipoprotein binding to schistosomula of Schistosoma mansoni. Displacement by polyanions, parasite antigen masking, and persistence in young larvae. The American Journal of Pathology 135, 1015–1024.Google ScholarPubMed
Cornford, E.M., Fitzpatrick, A.M., Quirk, T.L., Diep, C.P. & Landaw, E.M. (1988) Tegumental glucose permeability in male and female Schistosoma mansoni. Journal of Parasitology 74, 116–128.CrossRefGoogle ScholarPubMed
Dimmer, K.S., Friedrich, B., Lang, F., Deitmer, J.W. & Broer, S. (2000) The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochemistry Journal 350, 219–227.CrossRefGoogle Scholar
Faghiri, Z. & Skelly, P.J. (2009) The role of tegumental aquaporin from the human parasitic worm, Schistosoma mansoni, in osmoregulation and drug uptake. FASEB Journal 23, 2780–2789.CrossRefGoogle ScholarPubMed
Faghiri, Z., Camargo, S.M., Huggel, K., Forster, I.C., Ndegwa, D., Verrey, F. & Skelly, P.J. (2010) The tegument of the human parasitic worm Schistosoma mansoni as an excretory organ: the surface aquaporin SmAQP is a lactate transporter. PLoS One 5, e10451.CrossRefGoogle ScholarPubMed
Fripp, P.J. (1967a) The histochemical localization of leucine aminopeptidase activity in Schistosoma rodhaini. Comparative Biochemistry and Physiology B 20, 307–309.CrossRefGoogle Scholar
Fripp, P.J. (1967b) The sites of (1-14C)glucose assimilation in Schistosoma haematobium. Comparative Biochemistry and Physiology 23, 893–898.CrossRefGoogle Scholar
Githui, E.K., Damian, R.T. & Aman, R.A. (2006a) In vitro efflux of lactic acid by schistosomes cultured in varying concentrations of glucose: potential toxicity of accumulated lactic acid. Journal of Tropical Microbiology and Biotechnology 2, 31–36.CrossRefGoogle Scholar
Githui, E.K., Damian, R.T. & Aman, R.A. (2006b) Schistosoma mansoni: biochemical characterization of lactate transporters or similar proteins. Experimental Parasitology 114, 180–188.CrossRefGoogle ScholarPubMed
Gomme, J. & Albrechtsen, S. (1988) Problems of interpreting integumental D-glucose fluxes by the integument of Schistosoma. Comparative Biochemistry and Physiology A, Comparative Physiology 90, 651–657.CrossRefGoogle ScholarPubMed
Gonen, T. & Walz, T. (2006) The structure of aquaporins. Quarterly Review of Biophysics 39, 361–396.CrossRefGoogle ScholarPubMed
Gourbal, B., Sonuc, N., Bhattacharjee, H., Legare, D., Sundar, S., Ouellette, M., Rosen, B.P. & Mukhopadhyay, R. (2004) Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. Journal of Biological Chemistry 279, 31010–31017.CrossRefGoogle ScholarPubMed
Hockley, D.J. & McLaren, D.J. (1973) Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. International Journal for Parasitology 3, 13–25.CrossRefGoogle ScholarPubMed
Isseroff, H., Bonta, C.Y. & Levy, M.G. (1972) Monosaccharide absorption by Schistosoma mansoni. I. Kinetic characteristics. Comparative Biochemistry and Physiology A 43, 849–858.CrossRefGoogle ScholarPubMed
Jiang, J., Skelly, P.J., Shoemaker, C.B. & Caulfield, J.P. (1996) Schistosoma mansoni: the glucose transport protein SGTP4 is present in tegumental multilamellar bodies, discoid bodies, and the surface lipid bilayers. Experimental Parasitology 82, 201–210.CrossRefGoogle ScholarPubMed
Krautz-Peterson, G., Camargo, S., Huggel, K., Verrey, F., Shoemaker, C.B. & Skelly, P.J. (2007) Amino acid transport in schistosomes: characterization of the permease heavy chain SPRM1hc. Journal of Biological Chemistry 282, 21767–21775.CrossRefGoogle ScholarPubMed
Krautz-Peterson, G., Simoes, M., Faghiri, Z., Ndegwa, D., Oliveira, G., Shoemaker, C.B. & Skelly, P.J. (2010) Suppressing glucose transporter gene expression in schistosomes impairs parasite feeding and decreases survival in the mammalian host. PLoS pathogens 6, e1000932.CrossRefGoogle ScholarPubMed
Liu, Z. (2010) Roles of vertebrate aquaglyceroporins in arsenic transport and detoxification. Advances in Experimental Medicine and Biology 679, 71–81.CrossRefGoogle ScholarPubMed
Mastroberardino, L., Spindler, B., Pfeiffer, R., Skelly, P.J., Loffing, J., Shoemaker, C.B. & Verrey, F. (1998) Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature 395, 288–291.CrossRefGoogle ScholarPubMed
Morris, G.P. & Threadgold, L.T. (1968) Ultrastructure of the tegument of adult Schistosoma mansoni. Journal of Parasitology 54, 15–27.CrossRefGoogle ScholarPubMed
Ndegwa, D., Krautz-Peterson, G. & Skelly, P.J. (2007) Protocols for gene silencing in schistosomes. Experimental Parasitology 117, 284–291.CrossRefGoogle ScholarPubMed
Pereira, A.S., Padilha, R.J., Lima-Filho, J.L. & Chaves, M.E. (2011) Scanning electron microscopy of the human low-density lipoprotein interaction with the tegument of Schistosoma mansoni. Parasitology Research 109, 1395–1402.CrossRefGoogle ScholarPubMed
Pfeiffer, R., Spindler, B., Loffing, J., Skelly, P.J., Shoemaker, C.B. & Verrey, F. (1998) Functional heterodimeric amino acid transporters lacking cysteine residues involved in disulfide bond. FEBS Letters 439, 157–162.CrossRefGoogle ScholarPubMed
Rodriguez-Molina, R., Acevedo, C.E., Torres, J.M., Lopez-Sanabria, U. & Ramirez-Rodriguez, E. (1950) Treatment of schistosomiasis mansoni with antimony lithium thiomalate (Anthiomaline); final report. American Journal of Tropical Medicine and Hygiene 30, 881–886.CrossRefGoogle ScholarPubMed
Sanders, O.I., Rensing, C., Kuroda, M., Mitra, B. & Rosen, B.P. (1997) Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli. Journal of Bacteriology 179, 3365–3367.CrossRefGoogle ScholarPubMed
Shapiro, T.A. & Talalay, P. (1982) Schistosoma mansoni: mechanisms in regulation of glycolysis. Experimental Parasitology 54, 379–390.CrossRefGoogle ScholarPubMed
Silk, M.H., Spence, I.M. & Gear, J.H. (1969) Ultrastructural studies of the blood fluke – Schistosoma mansoni. I. The integument. South African Journal of Medical Sciences 34, 1–10.Google ScholarPubMed
Skelly, P. (2008) Fighting killer worms. Scientific American 298, 94–99.CrossRefGoogle ScholarPubMed
Skelly, P.J. & Shoemaker, C.B. (1996) Rapid appearance and asymmetric distribution of glucose transporter SGTP4 at the apical surface of intramammalian-stage Schistosoma mansoni. Proceedings of the National Academy of Sciences USA 93, 3642–3646.CrossRefGoogle ScholarPubMed
Skelly, P. & Wilson, R. (2006) Making sense of the schistosome surface. Advances in Parasitology 63, 185–284.CrossRefGoogle ScholarPubMed
Skelly, P., Cunningham, J., Kim, J. & Shoemaker, C. (1994) Cloning, characterization and functional expression of cDNAs encoding glucose transporter proteins from the human parasite, Schistosoma mansoni. Journal of Biological Chemistry 269, 4247–4253.CrossRefGoogle ScholarPubMed
Skelly, P.J., Tielens, A.G.M. & Shoemaker, C.B. (1998) Glucose transport and metabolism in mammalian stage schistosomes. Parasitology Today 14, 402–406.CrossRefGoogle ScholarPubMed
Skelly, P.J., Pfeiffer, R., Verrey, F. & Shoemaker, C.B. (1999) SPRM1lc, a heterodimeric amino acid permease light chain of the human parasitic platyhelminth, Schistosoma mansoni. Parasitology 119, 569–576.CrossRefGoogle ScholarPubMed
Smith, J.H., Reynolds, E.S. & Von Lichtenberg, F. (1969) The integument of Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 18, 28–49.CrossRefGoogle ScholarPubMed
Thompson, D.P., Morrison, D.D., Pax, R.A. & Bennett, J.L. (1984) Changes in glucose metabolism and cyanide sensitivity in Schistosoma mansoni during development. Molecular and Biochemical Parasitology 13, 39–51.CrossRefGoogle ScholarPubMed
Uglem, G.L. & Read, C.P. (1975) Sugar transport and metabolism in Schistosoma mansoni. Journal of Parasitology 61, 390–397.CrossRefGoogle ScholarPubMed
van Balkom, B.W., van Gestel, R.A., Brouwers, J.F., Krijgsveld, J., Tielens, A.G., Heck, A.J. & van Hellemond, J.J. (2005) Mass spectrometric analysis of the Schistosoma mansoni tegumental sub-proteome. Journal of Proteome Research 4, 958–966.CrossRefGoogle ScholarPubMed
Wilson, R.A. & Barnes, P.E. (1974a) An in vitro investigation of dynamic processes occurring in the schistosome tegument, using compounds known to disrupt secretory processes. Parasitology 68, 259–270.CrossRefGoogle Scholar
Wilson, R.A. & Barnes, P.E. (1974b) The tegument of Schistosoma mansoni: observations on the formation, structure and composition of cytoplasmic inclusions in relation to tegument function. Parasitology 68, 239–258.CrossRefGoogle Scholar
Zhao, F.Q. & Keating, A.F. (2007) Functional properties and genomics of glucose transporters. Current Genomics 8, 113–128.CrossRefGoogle ScholarPubMed
Zhong, C., Skelly, P.J., Leaffer, D., Cohn, R.G., Caulfield, J.P. & Shoemaker, C.B. (1995) Immunolocalization of a Schistosoma mansoni facilitated diffusion glucose transporter to the basal, but not the apical, membranes of the surface syncytium. Parasitology 110, 383–394.CrossRefGoogle Scholar