Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 144, Issue 1, Pages 44-54Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2005.07.006
Keywords
Apicomplexa; intracellular parasitism; BT1; membrane transporter; folate metabolism; folic acid
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Funding
- NIAID NIH HHS [AI 44630, AI05093, T32 AI07404, R01 AI46416, 1R0AI045806-01A1] Funding Source: Medline
- NIGMS NIH HHS [T32 GM07324, GMO7205] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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 methottexate, 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. (D 2005 Elsevier B.V. All rights reserved.
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