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J. Biol. Chem., Vol. 277, Issue 33, 29460-29467, August 16, 2002
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From the Centre de Recherche en Infectiologie du Centre de
Recherche du CHUL and Division de Microbiologie, Faculté de
Médecine, Université Laval,
Québec G1V 4G2, Canada
The protozoan parasite Leishmania is
a folate auxotroph and thus depends on the uptake of folate from the
environment to meet its folate requirement. We show here that
Leishmania contains several putative pteridine transporter
genes. Some of these genes are deleted in methotrexate-resistant
Leishmania cells where there is no measurable uptake of
methotrexate. Transport studies suggest that Leishmania has
more than one active folate transporter, and one of these, named
FT5, corresponds to a very high affinity folate transporter
(Km 84 nM). The uptake of both folate
and methotrexate was impaired in an FT5 null mutant at low
substrate concentrations (50 nM), although transport
properties at higher concentrations (1000 nM) were not
statistically different between wild-type and the FT5 null
mutant. Modulation of the expression of FT5 also changes the
susceptibility of Leishmania cells to methotrexate. These
results have permitted the characterization of a novel class of folate
transporters and suggest that the parasite Leishmania has
several gene products possibly transporting folates and related
molecules under varying conditions.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY099959 and AY099960.
A New Type of High Affinity Folic Acid Transporter in the
Protozoan Parasite Leishmania and Deletion of Its Gene in
Methotrexate-resistant Cells*
,
*
This work was supported in part by the Canadian Institutes
for Health Research (to M. O.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a studentship from Canadian Institutes for Health Research.
§
Postdoctoral fellow of the Schweizerisher National Funds.
¶
Canadian Institutes for Health Research Investigator and a
Burroughs Wellcome Fund Scholar in Molecular Parasitology. To whom correspondence should be addressed: Centre de Recherche en
Infectiologie, CHUQ, Pavillon CHUL, 2705 Blvd. Laurier, Ste-Foy,
Québec G1V 4G2, Canada. Tel.: 418-654-2705; Fax: 418-654-2715;
E-mail: Marc.Ouellette@crchul.ulaval.ca.
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