Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro
Peatey, Christopher L., Chavchich, Marina, Chen, Nanhua, Gresty, Karryn J., Gray, Karen-Ann, Gatton, Michelle L., Waters, Norman C., & Cheng, Qin (2015) Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro. Journal of Infectious Diseases, 212(3), pp. 426-434.
Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.
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|Item Type:||Journal Article|
|Additional Information:||First published online: January 29, 2015|
|Keywords:||Plasmodium falciparum, artemisinin, dihydroartemisinin (DHA), dormancy, mitochondrial membrane potential|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL MICROBIOLOGY (110800) > Medical Parasitology (110803)|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Public Health & Social Work
|Copyright Owner:||Copyright 2015 Oxford University Press|
|Deposited On:||21 Jan 2015 23:58|
|Last Modified:||05 Feb 2016 04:37|
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