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 K. Riscoe

doi:10.1016/j.molbiopara.2008.01.002

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 K. Riscoe

Molecular Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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 language	English (US)
Pages (from-to)	64-68
Number of pages	5
Journal	Molecular and Biochemical Parasitology
Volume	159
Issue number	1
DOIs	https://doi.org/10.1016/j.molbiopara.2008.01.002
State	Published - May 2008

Keywords

Complex III
Drug resistance
Electron transport
Malaria
Plasmodium

ASJC Scopus subject areas

Parasitology
Molecular Biology

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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 K.

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

Research output: Contribution to journal › Article › peer-review

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AU - Hinrichs, David J.

AU - Kramer, David M.

AU - Riscoe, Michael K.

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