A drug-selected Plasmodium falciparum lacking the need for conventional electron transport

Martin J. Smilkstein, Isaac Forquer, Atsuko Kanazawa, Jane Xu Kelly, Rolf W. Winter, David J. Hinrichs, David M. Kramer, Michael Riscoe

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Mitochondrial electron transport is essential for survival in Plasmodium falciparum, making the cytochrome (cyt) bc1 complex an attractive target for antimalarial drug development. Here we report that P. falciparum cultivated in the presence of a novel cyt bc1 inhibitor underwent a fundamental transformation in biochemistry to a phenotype lacking a requirement for electron transport through the cyt bc1 complex. Growth of the drug-selected parasite clone (SB1-A6) is robust in the presence of diverse cyt bc1 inhibitors, although electron transport is fully inhibited by these same agents. This transformation defies expected molecular-based concepts of drug resistance, has important implications for the study of cyt bc1 as an antimalarial drug target, and may offer a glimpse into the evolutionary future of Plasmodium.

Original languageEnglish (US)
Pages (from-to)64-68
Number of pages5
JournalMolecular and Biochemical Parasitology
Volume159
Issue number1
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Electron Transport Complex III
Plasmodium falciparum
Electron Transport
Pharmaceutical Preparations
Antimalarials
Plasmodium
Drug Resistance
Biochemistry
Parasites
Clone Cells
Phenotype
Growth

Keywords

  • Complex III
  • Drug resistance
  • Electron transport
  • Malaria
  • Plasmodium

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

A drug-selected Plasmodium falciparum lacking the need for conventional electron transport. / Smilkstein, Martin J.; Forquer, Isaac; Kanazawa, Atsuko; Kelly, Jane Xu; Winter, Rolf W.; Hinrichs, David J.; Kramer, David M.; Riscoe, Michael.

In: Molecular and Biochemical Parasitology, Vol. 159, No. 1, 05.2008, p. 64-68.

Research output: Contribution to journalArticle

Smilkstein, MJ, Forquer, I, Kanazawa, A, Kelly, JX, Winter, RW, Hinrichs, DJ, Kramer, DM & Riscoe, M 2008, 'A drug-selected Plasmodium falciparum lacking the need for conventional electron transport', Molecular and Biochemical Parasitology, vol. 159, no. 1, pp. 64-68. https://doi.org/10.1016/j.molbiopara.2008.01.002
Smilkstein, Martin J. ; Forquer, Isaac ; Kanazawa, Atsuko ; Kelly, Jane Xu ; Winter, Rolf W. ; Hinrichs, David J. ; Kramer, David M. ; Riscoe, Michael. / A drug-selected Plasmodium falciparum lacking the need for conventional electron transport. In: Molecular and Biochemical Parasitology. 2008 ; Vol. 159, No. 1. pp. 64-68.
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