Minireview
The apicoplast as an antimalarial drug target

https://doi.org/10.1054/drup.2001.0205Get rights and content

Abstract

Resistance to commonly used malaria drugs is spreading and new drugs are required urgently. The recent identification of a relict chloroplast (apicoplast) in malaria and related parasites offers numerous new targets for drug therapy using well-characterized compounds. The apicoplast contains a range of metabolic pathways and housekeeping processes that differ radically to those of the host thereby presenting ideal strategies for drug therapy. Indeed, many compounds targeting these plastid pathways are antimalarial and have favourable profiles based on extensive knowledge from their use as antibacterials.

References (72)

  • A.S Budimulja et al.

    The sensitivity of Plasmodium protein synthesis to prokaryotic ribosomal inhibitors

    Mol Biochem Parasitol

    (1997)
  • J. Harwood

    Recent advances in the biosynthesis of plant fatty-acids

    Biochim Biophys Acta

    (1996)
  • R.J. Heath et al.

    Enoyl-acyl carrier protein reductase (fabi) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli

    J Biol Chem

    (1995)
  • H.N. Bhargava et al.

    Triclosan: applications and safety

    American Journal of Infection Control

    (1996)
  • R.J. Heath et al.

    Mechanism of triclosan inhibition of bacterial fatty acid synthesis

    J Biol Chem

    (1999)
  • R.J. Heath et al.

    Broad spectrum antimicrobial biocides target the FabI component of fatty acid biosynthesis

    J Biol Chem

    (1998)
  • R.J. Heath et al.

    Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene

    J Biol Chem

    (2000)
  • G. Zhu et al.

    Molecular analysis of a Type I fatty acid synthase in Cryptosporidium parvum

    Mol Biochem Parasitol

    (2000)
  • A. Golz et al.

    Inhibitors of de novo fatty acid biosynthesis in higher plants

    J Plant Physiol

    (1994)
  • H.K. Lichtenthaler et al.

    Biosynthesis of isoprenoids in higher plant chloroplasts proceeds via a mevalonate-independent pathway

    FEBS Letters

    (1997)
  • B. Altincicek et al.

    Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa

    FEMS Microbiol Lett

    (2000)
  • N. Surolia et al.

    De novo biosynthesis of heme offers a new chemotherapeutic target in the human malarial parasite

    Biochem. Biophys Res Commun

    (1992)
  • S. Sato et al.

    Impact of a plastid-bearing endocytobiont on apicomplexan genomes

    Int J Parasitol

    (2000)
  • A.R.K. Prasad et al.

    Generation of resistance to the diphenyl ether herbicide acifluorfen by mel cells

    Biochem Biophys Re Commun

    (1995)
  • I. Macreadie et al.

    Antimalarial drug development and new targets

    Parasitology Today

    (2000)
  • M. Strath et al.

    Antimalarial activity of rifampicin in vitro and in rodent models

    Trans R Soc Trop Med Hyg

    (1993)
  • M. Sullivan et al.

    Effects of interruption of apicoplast function on malaria infection, development, and transmission

    Mol Biochem Parasitol

    (2000)
  • B. Clough et al.

    Antibiotic inhibitors of organellar protein synthesis in Plasmodium falciparum

    Protist

    (1999)
  • C.F. Delwiche et al.

    The origin of plastids and their spread via secondary endosymbiosis

    Pl Syst Evol

    (1997)
  • M.E. Fichera et al.

    A plastid organelle as a drug target in apicomplexan parasites

    Nature

    (1997)
  • C.Y. He et al.

    A plastid segregation defect in the protozoan parasite Toxoplasma gondii

    EMBO Journal

    (2001)
  • R.J.M. Wilson et al.

    Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum

    J Mol Biol

    (1996)
  • R. Gozalbes et al.

    Anti-Toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: Prediction of activity by molecular topology and virtual computational techniques

    Antimicrobial Agents & Chemotherapy

    (2000)
  • R.A. Walker et al.

    Use of a LightCycler gyrA mutation assay for rapid identification of mutations conferring decreased susceptibility to ciprofloxacin in multiresistant Salmonella enterica serotype typhimurium DT104 isolates

    J of Clin Microbiol

    (2001)
  • Y. Onodera et al.

    Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis

    J Antimicrob Chemother

    (2001)

    • Cited by (0)

    f1

    Correspondence to: Geoffrey I. McFadden, E-mail: [email protected]

    View full text
    Copyright © 2001 Harcourt Publishers Ltd. All rights reserved.