Toxoplasma gondii is capable of exogenous folate transport: A likely expansion of the BT1 family of transmembrane proteins

Kristen M. Massimine, Lanxuan T. Doan, Chloé A. Atreya, Timothy T. Stedman, Karen S. Anderson, Keith A. Joiner, Isabelle Coppens

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Folates are key elements in eukaryotic biosynthetic processes. The protozoan parasite Toxoplasma gondii possesses the enzymes necessary for de novo folate synthesis and has been suggested to lack alternative mechanisms for folate acquisition. In this paper, we present a different view by providing evidence that Toxoplasma is capable of salvaging exogenous folates. By monitoring uptake of radiolabeled folates by parasites in axenic conditions, our studies revealed a common folate transporter that has a high affinity for folic acid. Transport of this compound across the parasite plasma membrane is rapid, biphasic, temperature dependent, bi-directional, concentration dependent and specific. In addition, morphological evidence demonstrates that fluorescent methotrexate, a folate analog, is internalized by Toxoplasma and shows localization reminiscent to the mitochondrion. The presence of putative folate transporter genes in the Toxoplasma genome, which are homologous to the BT1 family of proteins, suggests that Toxoplasma may encode proteins involved in folate transport. Interestingly, genome analysis suggests that the BT1 family of proteins exists not only in Toxoplasma, but in other Apicomplexan parasites as well. Altogether, our results not only have implications for current therapeutic regimens against T. gondii, but they also allude that the folate transport mechanism may represent a novel Apicomplexan target for the development of new drugs.

Original languageEnglish (US)
Pages (from-to)44-54
Number of pages11
JournalMolecular and Biochemical Parasitology
Volume144
Issue number1
DOIs
StatePublished - Nov 1 2005

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Keywords

  • Apicomplexa
  • BT1
  • Folate metabolism
  • Folic acid
  • Intracellular parasitism
  • Membrane transporter

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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