Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasiteLeishmania major
10.1073/pnas.160257897
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Protozoan parasites of the genusLeishmaniaundergo a complex life cycle involving transmission by biting sand flies and replication within mammalian macrophage phagolysosomes. A major component of theLeishmaniasurface coat is the glycosylphosphatidylinositol (GPI)-anchored polysaccharide called lipophosphoglycan (LPG). LPG has been proposed to play many roles in the infectious cycle, including protection against complement and oxidants, serving as the major ligand for macrophage adhesion, and as a key factor mitigating host responses by deactivation of macrophage signaling pathways. However, all structural domains of LPG are shared by other major surface or secretory products, providing a biochemical redundancy that compromises the ability ofin vitrotests to establish whether LPG itself is a virulence factor. To study trulylpg−parasites, we generatedLeishmania majorlacking the geneLPG1[encoding a putative galactofuranosyl (Galf) transferase] by targeted gene disruption. Thelpg1−parasites lacked LPG but contained normal levels of related glycoconjugates and GPI-anchored proteins. Infections of susceptible mice and macrophagesin vitroshowed that theselpg−Leishmaniawere highly attenuated. Significantly and in contrast to previous LPG mutants, reintroduction ofLPG1into thelpg−parasites restored virulence. Thus, genetic approaches allow dissection of the roles of this complex family of interrelated parasite virulence factors, and definitively establish the role of LPG itself as a parasite virulence factor. Because thelpg1−mutant continue to synthesize bulk GPI-anchored Galf-containing glycolipids other than LPG, a second pathway distinct from the Golgi-associated LPG synthetic compartment must exist.

Bibliography

Späth, G. F., Epstein, L., Leader, B., Singer, S. M., Avila, H. A., Turco, S. J., & Beverley, S. M. (2000). Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasiteLeishmania major. Proceedings of the National Academy of Sciences, 97(16), 9258–9263.

Authors 7
  1. Gerald F. Späth (first)
  2. Linda Epstein (additional)
  3. Ben Leader (additional)
  4. Steven M. Singer (additional)
  5. Herbert A. Avila (additional)
  6. Salvatore J. Turco (additional)
  7. Stephen M. Beverley (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 10:41 a.m.)
Deposited 2 years, 4 months ago (April 22, 2023, 8:28 a.m.)
Indexed 10 hours, 29 minutes ago (Sept. 2, 2025, 6:35 a.m.)
Issued 25 years, 1 month ago (July 25, 2000)
Published 25 years, 1 month ago (July 25, 2000)
Published Online 25 years, 1 month ago (July 25, 2000)
Published Print 25 years, 1 month ago (Aug. 1, 2000)
Funders 0

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@article{Sp_th_2000, title={Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasiteLeishmania major}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.160257897}, DOI={10.1073/pnas.160257897}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Späth, Gerald F. and Epstein, Linda and Leader, Ben and Singer, Steven M. and Avila, Herbert A. and Turco, Salvatore J. and Beverley, Stephen M.}, year={2000}, month=jul, pages={9258–9263} }