A Nucleotide Sugar Transporter Involved in Glycosylation of the Toxoplasma Tissue Cyst Wall Is Required for Efficient Persistence of Bradyzoites

Carolina E. Caffaro, Anita A Koshy, Li Liu, Gusti M. Zeiner, Carlos B. Hirschberg, John C. Boothroyd

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Toxoplasma gondii is an intracellular parasite that transitions from acute infection to a chronic infective state in its intermediate host via encystation, which enables the parasite to evade immune detection and clearance. It is widely accepted that the tissue cyst perimeter is highly and specifically decorated with glycan modifications; however, the role of these modifications in the establishment and persistence of chronic infection has not been investigated. Here we identify and biochemically and biologically characterize a Toxoplasma nucleotide-sugar transporter (TgNST1) that is required for cyst wall glycosylation. Toxoplasma strains deleted for the TgNST1 gene (Δnst1) form cyst-like structures in vitro but no longer interact with lectins, suggesting that Δnst1 strains are deficient in the transport and use of sugars for the biosynthesis of cyst-wall structures. In vivo infection experiments demonstrate that the lack of TgNST1 activity does not detectably impact the acute (tachyzoite) stages of an infection or tropism of the parasite for the brain but that Δnst1 parasites are severely defective in persistence during the chronic stages of the infection. These results demonstrate for the first time the critical role of parasite glycoconjugates in the persistence of Toxoplasma tissue cysts.

Original languageEnglish (US)
Article numbere1003331
JournalPLoS Pathogens
Volume9
Issue number5
DOIs
StatePublished - May 2013

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Toxoplasma
Glycosylation
Cysts
Parasites
Nucleotides
Infection
Tropism
Glycoconjugates
Lectins
Polysaccharides
Brain
Genes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

A Nucleotide Sugar Transporter Involved in Glycosylation of the Toxoplasma Tissue Cyst Wall Is Required for Efficient Persistence of Bradyzoites. / Caffaro, Carolina E.; Koshy, Anita A; Liu, Li; Zeiner, Gusti M.; Hirschberg, Carlos B.; Boothroyd, John C.

In: PLoS Pathogens, Vol. 9, No. 5, e1003331, 05.2013.

Research output: Contribution to journalArticle

Caffaro, Carolina E. ; Koshy, Anita A ; Liu, Li ; Zeiner, Gusti M. ; Hirschberg, Carlos B. ; Boothroyd, John C. / A Nucleotide Sugar Transporter Involved in Glycosylation of the Toxoplasma Tissue Cyst Wall Is Required for Efficient Persistence of Bradyzoites. In: PLoS Pathogens. 2013 ; Vol. 9, No. 5.
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