Glycosylphosphatidylinositols are required for the development of Trypanosoma cruzi amastigotes

Nisha Garg, M. Postan, K. Mensa-Wilmot, R. L. Tarleton

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Induction of a glycosylphosphatidylinositol (GPI) deficiency in Trypanosoma cruzi by the heterologous expression of Trypanosoma brucei GPI- phospholipase C (GPI-PLC) results in decreased expression of major surface proteins (N. Garg, R. L. Tarleton, and K. Mensa-Wilmot, J. Biol. Chem. 272:12482-12491, 1997). To further explore the consequences of a GPI deficiency on replication and differentiation of T. cruzi, the in vitro and in vivo behaviors of GPI-PLC-expressing T. cruzi were studied. In comparison to wild-type controls, GPI-deficient T. cruzi epimastigotes exhibited a slight decrease in overall growth potential in culture. In the stationary phase of in vitro growth, GPI-deficient epimastigotes readily converted to metacyclic trypomastigotes and efficiently infected mammalian cells. However, upon conversion to amastigote forms within these host cells, the GPI- deficient parasites exhibited a limited capacity to replicate and subsequently failed to differentiate into trypomastigotes. Mice infected with GPI-deficient parasites showed a substantially lower rate of mortality, decreased tissue parasite burden, and a moderate tissue inflammatory response in comparison to those of mice infected with wild-type parasites. The decreased virulence exhibited by GPI-deficient parasites suggests that inhibition of GPI biosynthesis is a feasible strategy for chemotherapy of infections by T. cruzi and possibly other intracellular protozoan parasites.

Original languageEnglish (US)
Pages (from-to)4055-4060
Number of pages6
JournalInfection and Immunity
Volume65
Issue number10
StatePublished - Oct 1997
Externally publishedYes

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Glycosylphosphatidylinositols
Trypanosoma cruzi
Parasites
Trypanosoma brucei brucei
Type C Phospholipases
Growth
Virulence
Membrane Proteins
Drug Therapy
Mortality
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Glycosylphosphatidylinositols are required for the development of Trypanosoma cruzi amastigotes. / Garg, Nisha; Postan, M.; Mensa-Wilmot, K.; Tarleton, R. L.

In: Infection and Immunity, Vol. 65, No. 10, 10.1997, p. 4055-4060.

Research output: Contribution to journalArticle

Garg, N, Postan, M, Mensa-Wilmot, K & Tarleton, RL 1997, 'Glycosylphosphatidylinositols are required for the development of Trypanosoma cruzi amastigotes', Infection and Immunity, vol. 65, no. 10, pp. 4055-4060.
Garg, Nisha ; Postan, M. ; Mensa-Wilmot, K. ; Tarleton, R. L. / Glycosylphosphatidylinositols are required for the development of Trypanosoma cruzi amastigotes. In: Infection and Immunity. 1997 ; Vol. 65, No. 10. pp. 4055-4060.
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