+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Characterisation of exogenous folate transport in Plasmodium falciparum

Characterisation of exogenous folate transport in Plasmodium falciparum

Molecular and Biochemical Parasitology 154(1): 40-51

Folate salvage by Plasmodium falciparum is an important source of key cofactors, but little is known about the underlying mechanism. Using synchronised parasite cultures, we observed that uptake of this dianionic species against the negative-inward electrochemical gradient is highly dependent upon cell-cycle stage, temperature and pH, but not on mono- or divalent metal ions. Energy dependence was tested with different sugars; glucose was necessary for folate import, although fructose was also able to function in this role, unlike sugars that cannot be processed through the glycolytic pathway. Import into both infected erythrocytes and free parasites was strongly inhibited by the anion-channel blockers probenecid and furosemide, which are likely to be acting predominantly on specific folate transporters in both cases. Import was not affected by high concentrations of the antifolate drugs pyrimethamine and sulfadoxine, but was inhibited by the close folate analogue methotrexate. The pH optimum for folate uptake into infected erythrocytes was 6.5-7.0. Dinitrophenol and nigericin, which strongly facilitate the equilibration of H(+) ions across biological membranes and thus abolish or substantially reduce the proton gradient, inhibited folate uptake profoundly. The ATPase inhibitor concanamycin A also greatly reduced folate uptake, further demonstrating a link to ATP-powered proton transport. These data strongly suggest that the principal folate uptake pathway in P. falciparum is specific, highly regulated, dependent upon the proton gradient across the parasite plasma membrane, and is likely to be mediated by one or more proton symporters.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 013980771

Download citation: RISBibTeXText

PMID: 17509698

DOI: 10.1016/j.molbiopara.2007.04.002

Related references

Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy. Molecular Microbiology 32(6): 1254-1262, 1999

MRP1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum. Febs Letters 590(4): 482-492, 2016

The molecular basis of folate salvage in Plasmodium falciparum: characterization of two folate transporters. Journal of Biological Chemistry 286(52): 44659-44668, 2012

Characterisation of the rhoph2 gene of Plasmodium falciparum and Plasmodium yoelii. Molecular and Biochemical Parasitology 127(1): 47-57, 2003

Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation. Molecular Nutrition & Food Research 60(6): 1501-1513, 2016

Folate and cobalamin metabolism in Plasmodium falciparum. Parasitology Today 6(12): 388-391, 1990

Exploring the folate pathway in Plasmodium falciparum. Acta Tropica 94(3): 191-206, 2005

Inhibitors of de novo folate enzymes in Plasmodium falciparum. Drug Discovery Today 11(19-20): 939-944, 2006

Cross serological reactions between Plasmodium falciparum and Plasmodium cynomolgi Bastianellii. Application to the serodiagnosis, by immunofluorescence, of human Plasmodium falciparum malaria. Bulletin de la Societe de Pathologie Exotique et de Ses Filiales 59(3): 316-325, 1966

Use a monoclonal anti plasmodium berghei antibody cross reacting with plasmodium falciparum for the detection of plasmodium falciparum in in vitro infected blood. Immunology Letters 10(1): 31-34, 1985

Comparison of the Clinical Profile and Complications of Mixed Malarial Infections of Plasmodium Falciparum and Plasmodium Vivax versus Plasmodium Falciparum Mono-infection. Sultan Qaboos University Medical Journal 11(3): 377-382, 2011

Comparative analysis at the nucleotide level of the genes encoding the lactate dehydrogenase enzyme of Plasmodium vivax and Plasmodium falciparum Plasmodium vivax ve Plasmodium falciparum un laktat dehidrogenaz enzimini kodlayan genlerinin nukleotid duzeyinde karsilastirmali analizi. Turkiye Parazitoloji Dergisi, 293: 149-153, 2005

Reactions serologiques croisees entre Plasmodium falciparum et Plasmodium cynomolgi bastianellii. Applications au sero-diagnostic, par immunofluorescence, du paludisme humain a Plasmodium falciparum. Bulletin de la Societe de Pathologie Exotique, 59: 316-325, 1966

Cross serologic reactions between plasmodium falciparum and plasmodium cynomolgi bastianellii applications to the immuno fluorescence sero diagnosis of human malaria due to plasmodium falciparum. Bulletin de la Societe de Pathologie Exotique 59(3): 316-325, 1966, 1967

Antibodies to plasmodium falciparum ring infected erythrocyte surface antigen and plasmodium falciparum and plasmodium vivax circumsporozoite proteins. Medical Science Research 19(11): 345-350, 1991