Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-22T23:21:20.290Z Has data issue: false hasContentIssue false
  • English
  • Français

Characterization of phosphoglycan-containing secretory products of Leishmania

Published online by Cambridge University Press:  06 April 2009

T. Ilg ,
Y.-D. Stierhof ,
M. Wiese ,
M. J. McConville  and
P. Overath
T. Ilg
Affiliation:
Max-Planck-Institut für Biologic, Abteilung Membranbiochemie Corrensstrasse 38, D72076 Tübingen, Germany
Y.-D. Stierhof
Affiliation:
Max-Planck-Institut für Biologic, Abteilung Membranbiochemie Corrensstrasse 38, D72076 Tübingen, Germany
M. Wiese
Affiliation:
Max-Planck-Institut für Biologic, Abteilung Membranbiochemie Corrensstrasse 38, D72076 Tübingen, Germany
M. J. McConville
Affiliation:
Department of Biochemistry, University of Dundee, Dundee DD1 4HN, UK
P. Overath
Affiliation:
Max-Planck-Institut für Biologic, Abteilung Membranbiochemie Corrensstrasse 38, D72076 Tübingen, Germany
Get access Rights & Permissions [Opens in a new window]

Summary

This article presents an overview on phosphoglycan-containing components secreted by the insect and mammalian stages of several species of Leishmania, the causative agents of leishmaniasis in the Old and New World. Firstly, promastigotes of all three species considered, L. mexicana, L. donovani and L. major, shed lipophosphoglycan (LPG) into the culture medium possibly by release of micelles from the cell surface. Like the cell-associated LPG, culture supernatant LPG is arhphiphilic and composed of a lysoalkylphosphatidylinositol-phosphosaccharide core connected to species-specific phosphosaccharide repeats and oligosaccharide caps. Secondly, all three species release hydrophilic phosphoglycan. Thirdly, all three species appear to secrete proteins covalently modified by phosphosaccharide repeats and oligosaccharide caps. In the case of promastigotes of L. mexicana, these components are organized as two filamentous polymers released from the flagellar pocket: the secreted acid phosphatase (sAP) composed of a 100 kDa phosphoglycoprotein and a protein- containing high-molecular-weight-phosphoglycan (proteo-HMWPG) and fibrous networks likewise composed of phosphoglycan possibly linked to protein. Structural analyses and gene cloning suggest that the parasites can covalently modify protein regions rich in serine and threonine residues by the attachment of phosphosaccharide repeats capped by oligosaccharides. We propose that the networks formed in vitro correspond to fibrous material previously demonstrated in the digestive tract of infected sandflies. In the case of L. donovani, the sAP is also modified by phosphoglycans but contains neither proteo-HMWPG nor does it aggregate to filaments. Finally, L. mexicana amastigotes release proteo-HMWPG via the flagellar pocket into the parasitophorous vacuole of infected macrophages. This material appears to be released into the tissue of the infected mammal upon rupture of infected macrophages during lesion development. This secretory product may contribute to the pathology of lesion development.

Keywords

Leishmaniasecretionlipophosphoglycansecreted acid phosphataseproteo-high-molecular-weight phosphoglycanflagellar pocketparasitophorous vacuole.
Type
Research Article
Information
Parasitology , Volume 108 , supplement S1: Symposia of the British Society for Parasitology Volume 31:Functional molecules on the surface of protozoan parasites , March 1994 , pp. S63 - S71
Copyright
Copyright © Cambridge University Press 1994

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alexander, J. & Russell, D. G. (1992). The interaction of Leishmania species with macrophages. Advances in Parasitology 31, 175–254.CrossRefGoogle ScholarPubMed
Bahr, V., Stierhof, Y.-D., Ilg, T., Demar, M., Quinten, M. & Overath, P. (1993). Expression of lipophosphoglycan, high-molecular weight phosphoglycan and glycoprotein 63 in promastigotes and amastigotes of Leishmania mexicana. Molecular and Biochemical Parasitology 58, 107–22.CrossRefGoogle ScholarPubMed
Bates, P. A. & Dwyer, D. M. (1987). Biosynthesis and secretion of acid phosphatase by Leishmania donovani promastigotes. Molecular and Biochemical Parasitology 26, 289–96.CrossRefGoogle ScholarPubMed
Bates, P. A., Gottlieb, M. & Dwyer, D. M. (1988). Leishmania donovani: identification of glycoproteins released by promastigotes during growth in vitro. Experimental Parasitology 67, 199–209.CrossRefGoogle ScholarPubMed
Bates, P. A., Hermes, I. & Dwyer, D. M. (1989). Leishmania donovani: immunochemical localization and secretory mechanism of soluble acid phosphatase. Experimental Parasitology 68, 335–46.CrossRefGoogle ScholarPubMed
Bates, P. A., Hermes, I. & Dwyer, D. M. (1990). Golgimediated posttranslational processing of secretory acid phosphatase by Leishmania donovani promastigotes. Molecular and Biochemical Parasitology 39, 247—56.CrossRefGoogle ScholarPubMed
Bates, P. A., Kurtz, M. K., Gottlieb, M. & Dwyer, D. M.(1987). Leishmania donovani: generation of monospecific antibody reagents to soluble acid-phosphatase. Experimental Parasitology 64, 157—64.CrossRefGoogle ScholarPubMed
Bates, P. A. & Tetley, L. (1993). Leishmania mexicana: induction of metacyclogenesis by cultivation of promastigotes at acidic pH. Experimental Parasitology 76, 412–23.CrossRefGoogle ScholarPubMed
Bordier, C. (1987). The promastigote surface protease of Leishmania. Parasitology Today 3, 151—3.CrossRefGoogle ScholarPubMed
Bordier, C. (1988). Analytical and preparative phase separation of glycolipid-anchored membrane proteins in Triton X-114 solution. In Posttranslational Modification of Proteins by Lipids. A Laboratory Manual (ed. Brodbeck, U. & Bordier, C.), pp. 29–33. Heidelberg: Springer-Verlag.CrossRefGoogle Scholar
El-On, J. & Schnur, L. F. (1974). Purification and preliminary characterization of leishmanial excreted factors (EF). Journal of Protozoology (Suppl.) 21, 463–4.Google Scholar
El-On, J., Schnur, L. F. & Greenblatt, C. L. (1979). Leishmania donovani: physicochemical, immunological, and biological characterization of excreted factor from promastigotes. Experimental Parasitology 47, 254–69.CrossRefGoogle ScholarPubMed
Greis, K. D., Turco, S. J., Thomas, J. R., McConville, M. J., Homans, S. W. & Ferguson, M. A. J. (1992). Purification and characterization of an extracellular phosphoglycan from Leishmania donovani. Journal of Biological Chemistry 267, 5876–81.CrossRefGoogle ScholarPubMed
Handman, E. & Coding, J. W. (1985). The Leishmania receptor for macrophages is a lipid-containing glycoconjugate. EMBO Journal 4, 329–36.CrossRefGoogle ScholarPubMed
Handman, E., Greenblatt, C. L. & Coding, J. W. (1984). An amphipathic sulphated glycoconjugate of Leishmania: characterization with monoclonal antibodies. EMBO Journal 3, 2301–6.CrossRefGoogle ScholarPubMed
Ilg, T. (1992). Sekretierte Antigene von Leishmania Promastigoten: strukturelle und biochemische Charakterisierung von Lipophosphoglycan und sekretierter saurer Phosphatase. Ph.D. thesis, Universitat Tubingen.Google Scholar
Ilg, T., Etges, R., Overath, P., McConville, M. J., Thomas-Oates, J., Thomas, J., Homans, S. W. & Ferguson, M. A. J. (1992). Structure of Leishmania mexicana lipophosphoglycan. Journal of Biological Chemistry 267, 6834–40.CrossRefGoogle ScholarPubMed
Ilg, T., Harbecke, D. & Overath, P. (1993 a). The lysosomal gp63-related protein in Leishmania mexicana amastigotes is a soluble metalloproteinase with an acidic pH optimum. FEES Letters 327, 103–7.CrossRefGoogle ScholarPubMed
Ilg, T., Harbecke, D., Wiese, M. & Overath, P. (1993 b).Monoclonal antibodies directed against Leishmania secreted acid phosphatase and lipophosphoglycan: partial characterization of private and public epitopes. European Journal of Biochemistry 217, 603—15.CrossRefGoogle ScholarPubMed
Ilg, T., Menz, B., Winter, G., Russell, D. C., Etges, R., Schell, D. & Overath, P. (1991 a). Monoclonal antibodies to Leishmania mexicana promastigote antigens. I. Secreted acid phosphatase and other proteins share epitopes with lipophosphoglycan. Journal of Cell Science 99, 175–80.CrossRefGoogle ScholarPubMed
Ilg, T., Stierhof, Y.-D., Etges, R., Adrian, M., Harbecke, D. & Overath, P. (1991 b). Secreted acid phosphatase of Leishmania mexicana: a filamentous phosphoglycoprotein polymer. Proceedings of the National Academy of Sciences USA 88, 8774–8.CrossRefGoogle ScholarPubMed
Jaffe, C. L., Perez, L. M. & Schnur, L. F. (1990). Lipophosphoglycan and secreted acid phosphatase of Leishmania tropica share species-specific epitopes. Molecular and Biochemical Parasitology 41, 233–40.CrossRefGoogle ScholarPubMed
Kaneshiro, E. S., Dwyer, D. M. & Gottlieb, M. (1981). Shed membrane antigens from Leishmania promastigote cultures. Journal of Cell Biology 91, 250a.Google Scholar
Kaneshiro, E. S., Gottlieb, M. & Dwyer, D. M. (1982 a). Cell surface origin of antigens shed by Leishmania donovani during growth in axenic culture. Infection and Immunity 37, 558–67.CrossRefGoogle ScholarPubMed
Kaneshiro, E. S., Gottlieb, M. & Dwyer, D. M. (1982 b). Partial characterization of the major shed membrane antigens (SMA) from Leishmania donovani promastigote cultures. Journal of Protozoology 29, 471.Google Scholar
Killick-Kendrick, R., Wallbanks, K. R., Molyneux, D. H. & Lavin, D. R. (1988). The ultrastructure of Leishmania major in the foregut and proboscis of Phlebotomus papatasi. Parasitology Research 74, 586–90.CrossRefGoogle ScholarPubMed
King, D. L., Chang, Y. D. & Turco, S. J. (1987). Cell surface lipophosphoglycan of Leishmania donovani. Molecular and Biochemical Parasitology 24, 47–53.CrossRefGoogle ScholarPubMed
Lang, T., Warburg, A., Sacks, D. L., Croft, S. L., Lane, R. P. & Blackwell, J. M. (1991). Transmission and scanning EM- immunogold labeling of Leishmania major lipophosphoglycan in the sandfly Phlebotomus papatasi. European Journal of Cell Biology 55, 362–72.Google ScholarPubMed
Lovelace, J. K., Dwyer, D. M. & Gottlieb, M. (1986). Purification and characterization of the extracellular acid phosphatase of Leishmania donovani. Molecular and Biochemical Parasitology 20, 243–51.CrossRefGoogle ScholarPubMed
Lovelace, J. D. & Gottlieb, M. (1986). Comparison of extracellular acid phosphatase from various isolates of Leishmania. American Journal of Tropical Medicine and Hygiene 35, 1121–8.CrossRefGoogle ScholarPubMed
Lovelace, J. K. & Gottlieb, M. (1987 a). Effect of tunicamycin on the extracellular acid phosphatase of Leishmania donovani promastigotes. Molecular and Biochemical Parasitology 22, 19–28.CrossRefGoogle ScholarPubMed
Lovelace, J. K. & Gottlieb, M. (1987 b). Evidence for phosphorylation of the extracellular acid phosphatase of Leishmania donovani. Journal of Protozoology 34, 78–9.CrossRefGoogle ScholarPubMed
Mallinson, D. J. & Coombs, G. H. (1989). Biochemical characteristics of the metacyclic forms of Leishmania major and Leishmania mexicana mexicana. Parasitology 98, 7–15.CrossRefGoogle Scholar
McConville, M. J. & Bacic, A. (1989). A family of glycoinositol phospholipids from Leishmania major: isolation, characterization and antigenicity. Journal of Biological Chemistry 264, 757–66.CrossRefGoogle ScholarPubMed
McConville, M. J. & Bacic, A. (1990). The glycoinositolphospholipid profiles of two Leishmania major strains that differ in lipophosphoglycan expression. Molecular and Biochemical Parasitology 38, 57–67.CrossRefGoogle ScholarPubMed
McConville, M. J. & Blackwell, J. M. (1991).Developmental changes in the glycosylated phosphatidylinositols of Leishmania donovani. Characterization of the promastigote and amastigote glycolipids. Journal of Biological Chemistry 266, 15170–9.CrossRefGoogle ScholarPubMed
McConville, M. J., Homans, S. W., Thomas-Oates, J. E., Dell, A. & Bacic, A. (1990). Structures of the glycoinositolphospholipids from Leishmania major. A family of novel galactofuranose-containing glycolipids. Journal of Biological Chemistry 265, 7385–94.CrossRefGoogle ScholarPubMed
Medina-Acosta, E., Beverley, S. M. & Russell, D. G. (1993). Evolution and expression of the Leishmania surface proteinase (gp63) gene locus. Infectious Agents and Disease 2, 25–34.Google ScholarPubMed
Moody, S. F., Handman, E. & Bacic, A. (1991). Structure and antigenicity of the lipophosphoglycan from Leishmania major amastigotes. Glycobiology 1, 419–24.CrossRefGoogle ScholarPubMed
Pimenta, P. F. P., Turco, S. J., McConville, M. J., Lawyer, P. G., Perkins, P. V. & Sacks, D. L. (1992).Stage-specific adhesion of Leishmania promastigotes to the sandfly midgut. Science 256, 1812–15.CrossRefGoogle Scholar
Russell, D. G., Ip, H. S. & Medina-Acosta, E. (1991).Biology of the Leishmania surface protease, gp63. “Molecular and Immunological Aspects of Parasitism”. American Association for the Advancement of Science, 73–85.Google Scholar
Sacks, D. L. (1989). Metacyclogenesis in Leishmania promastigotes. Experimental Parasitology 69, 100–3.CrossRefGoogle ScholarPubMed
Schneider, P., Rosat, J. P., Bouvier, J., Louis, J. & Ordier, C. (1992). Leishmania major: differential regulation of the surface metalloprotease in amastigote and promastigote stages. Experimental Parasitology 75, 196–206.CrossRefGoogle ScholarPubMed
Schnur, L. F., Sarfstein, R. & Jaffe, C. L. (1990). Monoclonal antibodies against leishmanial membranes react with specific excreted factor (EF). Annals of Tropical Medicine and Parasitology 84, 447—56.CrossRefGoogle Scholar
Schnur, L. F., Zuckerman, A. & Greenblatt, C. L. (1972). Leishmanial serotypes as distinguished by the gel diffusion of factors excreted in vitro and in vivo. Israel Journal of Medical Sciences 8, 932–42.Google ScholarPubMed
Slutzky, G. M., El-On, J. & Greenblatt, C. L. (1979). Leishmanial excreted factor: protein-bound and free forms from promastigote cultures of Leishmania tropica and Leishmania donovani. Infection and Immunity 26, 916–26.CrossRefGoogle ScholarPubMed
Slutzky, G. M. & Greenblatt, C. L. (1977). Isolation of a carbohydrate-rich immunologically active factor from cultures of Leishmania tropica. FEBS Letters 80, 401–4.CrossRefGoogle ScholarPubMed
Slutzky, G. M. & Greenblatt, C. L. (1982). Identification of galactose as the immunodominant sugar of leishmanial excreted factor and subsequent labeling with galactose oxidase and sodium boro[3H]hydride. Infection and Immunity 37, 10—14.CrossRefGoogle Scholar
Stierhof, Y. D., Ilg, T., Russell, D. G., Hohenberg, H. & Overath, P. (1994). Characterization of polymer release from the flagellar pocket of Leishmania mexicana promastigotes. Journal of Cell Biology, in press.CrossRefGoogle ScholarPubMed
Stierhof, Y. D., Schwarz, H., Menz, B., Russell, D. G., Quinten, M. & Overath, P. (1991). Monoclonal antibodies to Leishmania mexicana promastigote antigens. II. Cellular localization of antigens in promastigotes and infected macrophages. Journal of Cell Science 99, 181–6.CrossRefGoogle ScholarPubMed
Talamas-Rohana, P., Wright, S. D., Lennartz, M. R. & Russell, D. G. (1990). Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150.95 and LFA 1 family of leukocyte integrins. Journal of Immunology 144, 4817–24.CrossRefGoogle ScholarPubMed
Tolson, D. L., Turco, S. J. & Pearson, T. W. (1990). Expression of a repeating phosphorylated disaccharide lipophosphoglycan epitope on the surface of macrophages infected with Leishmania donovani. Infection and Immunity 58, 3500–7.CrossRefGoogle ScholarPubMed
Turco, S. J. & Descoteaux, A. (1992). The lipophosphoglycan of Leishmania parasites. Annual Review of Microbiology 46, 65—94.CrossRefGoogle ScholarPubMed
Walters, L. L., Modi, G. B., Tesh, R. B. & Burrage, T. (1987). Host-parasite relationship of Leishmania mexicana mexicana and Lutzomyia abonnenci (Diptera, Psychodidae). American Journal of Tropical Medicine and Hygiene 36, 294–314.CrossRefGoogle ScholarPubMed
Webster, P. & Russell, D. G. (1993). The flagellar pocket of trypanosomatids. Parasitology Today 9, 201–6.CrossRefGoogle ScholarPubMed
Winter, G. (1993). Oberflächenantigene von Leishmania mexicana Amastigoten: Identifizierung und strukturelle Charakterisierung. Ph.D. thesis, Universitat Tubingen.Google Scholar
Zehavi, U., Abrahams, J. C., Granoth, R., Greenblatt, C. L., Slutzky, G. M. & El-On, J. (1983). Leishmanial excreted factors (EFs): purification by affinity chromatography. Zeitschrift für Parasitenkunde 69, 695–701.CrossRefGoogle ScholarPubMed