Journal article
Mitochondrial Electron Transport Inhibition and Viability of Intraerythrocytic Plasmodium falciparum
Antimicrobial agents and chemotherapy, v 54(12), pp 5281-5287
Dec 2010
PMID: 20855748
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although mitochondrial electron transport is a validated target of the antimalarial drug atovaquone, the molecular details underlying parasite demise are unclear. We have shown that a critical function of mitochondrial electron transport in blood-stage
Plasmodium falciparum
is to support pyrimidine biosynthesis. Here, we explore the effects of atovaquone, alone and in combination with proguanil, on
P. falciparum
viability. Our results suggest that the effects of inhibition depend upon the erythrocytic stage of the parasites and the duration of exposure. Ring- and schizont-stage parasites are most resilient to drug treatment and can survive for 48 h, with a fraction remaining viable even after 96 h. Survival of parasites does not appear to require nutrient uptake. Thus, intraerythrocytic parasites with inhibited mitochondrial electron transport and collapsed mitochondrial membrane potential do not undergo apoptosis but enter an apparent static state. These results have significant implications for desirable properties of antimalarials under development that target mitochondrial functions.
Metrics
Details
- Title
- Mitochondrial Electron Transport Inhibition and Viability of Intraerythrocytic Plasmodium falciparum
- Creators
- Heather J Painter - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaJoanne M Morrisey - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PennsylvaniaAkhil B Vaidya - Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Antimicrobial agents and chemotherapy, v 54(12), pp 5281-5287
- Publisher
- American Society for Microbiology (ASM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000284158000045
- Scopus ID
- 2-s2.0-78649672277
- Other Identifier
- 991014877964604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy