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 | |
| State | Published - May 2008 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A drug-selected Plasmodium falciparum lacking the need for conventional electron transport
AU - Smilkstein, Martin J.
AU - Forquer, Isaac
AU - Kanazawa, Atsuko
AU - Kelly, Jane Xu
AU - Winter, Rolf W.
AU - Hinrichs, David J.
AU - Kramer, David M.
AU - Riscoe, Michael
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - Complex III
KW - Drug resistance
KW - Electron transport
KW - Malaria
KW - Plasmodium
UR - http://www.scopus.com/inward/record.url?scp=41549117120&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41549117120&partnerID=8YFLogxK
U2 - 10.1016/j.molbiopara.2008.01.002
DO - 10.1016/j.molbiopara.2008.01.002
M3 - Article
C2 - 18308406
AN - SCOPUS:41549117120
VL - 159
SP - 64
EP - 68
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
SN - 0166-6851
IS - 1
ER -