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Exploring the folate pathway in Plasmodium falciparum.

John E Hyde1

  • 1Faculty of life Sciences, University of Manchester, P.O. Box 88, Manchester M60 1QD, UK. john.hyde@manchester.ac.uk

Acta Tropica
|April 23, 2005
PubMed
Summary

Antifolate drugs are crucial for combating malaria, especially Plasmodium falciparum, despite growing resistance. This review examines the folate pathway and antifolate resistance mechanisms, focusing on parasite biosynthesis versus salvage.

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Characterisation of the bifunctional dihydrofolate synthase-folylpolyglutamate synthase from Plasmodium falciparum; a potential novel target for antimalarial antifolate inhibition.

Molecular and biochemical parasitology·2010

Area of Science:

  • Malariology
  • Drug Resistance
  • Biochemistry

Background:

  • Antimalarial drug intervention remains primary despite increasing parasite resistance.
  • Plasmodium falciparum malaria causes significant mortality and socioeconomic burden.
  • Antifolates target dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in the folate pathway.

Purpose of the Study:

  • To review the folate metabolic pathway and antifolate drug resistance.
  • To emphasize the balance between parasite folate biosynthesis and exogenous folate salvage.
  • To explore potential new drug targets within the folate pathway.

Main Methods:

  • Review of existing literature on antifolate mechanisms and resistance.
  • Analysis of the folate metabolic pathway in Plasmodium parasites.

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  • Examination of parasite folate biosynthesis versus salvage strategies.

    • Main Results:

    • Antifolates are vital, inexpensive treatments for chloroquine-resistant malaria.
    • Drug resistance necessitates a deeper understanding of the folate pathway.
    • The interplay between parasite folate synthesis and salvage is critical for drug efficacy.

    Conclusions:

    • Understanding antifolate resistance is key to developing new antimalarial strategies.
    • Targeting novel enzymes in the folate pathway offers potential therapeutic avenues.
    • Balancing parasite folate metabolism is crucial for effective malaria control.