Roles of free GPIs in amastigotes of Leishmania

Kojo Mensa-Wilmot, Nisha Garg, Bradford S. McGwire, Hong Gang Lu, Li Zhong, Dora Abena Armah, Jonathan H. LeBowitz, Kwang Poo Chang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Glycosylated phosphatidylinositols (GPIs) are abundant cell surface molecules of the Leishmania. Amastigote-specific GPIs AmGPI-Y and AmGPI-Z, both ethanolamine (EtN)-containing glycolipids, were identified in Leishmania amazonensis. A paucity of GPI-anchored proteins in amastigotes of L. amazonensis made the kinetoplastid suitable for evaluating the importance of free (i.e. unconjugated to protein or polysaccharide) GPIs. A strain deficient in both AmGPI-Y and AmGPI-Z was produced by stable transfection of wild-type Leishmania with a GPI-phospholipase C gene. Phosphatidylinositol deficiency was not detected in the transfectants. GPI-deficient promastigotes infected murine macrophages in vitro and differentiated into amastigotes whose growth was arrested within the host cells. Cytostasis of amastigotes was also observed during axenic culture of GPI-deficient parasites. In a hamster model of leishmaniasis, GPI-deficient promastigotes produced smaller lesions with 20-fold fewer amastigotes than infections with control parasites. Together, these observations indicate that EtN-GPIs may be essential for amastigote viability, replication, and/or virulence. Implicit in these observations is the notion that drugs targeted against the GPI biosynthetic pathway might be of value in the management of human leishmaniasis. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)103-116
Number of pages14
JournalMolecular and Biochemical Parasitology
Volume99
Issue number1
DOIs
StatePublished - Mar 5 1999
Externally publishedYes

Keywords

  • Glycosylated phosphatidylinositols
  • Leishmania amazonensis
  • Replication
  • Viability

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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