The NTP generating activity of pyruvate kinase II is critical for apicoplast maintenance in plasmodium falciparum
- Johns Hopkins Bloomberg School of Public Health, United States
Abstract
The apicoplast of Plasmodium falciparum parasites is believed to rely on the import of three-carbon phosphate compounds for use in organelle anabolic pathways, in addition to the generation of energy and reducing power within the organelle. We generated a series of genetic deletions in an apicoplast metabolic bypass line to determine which genes involved in apicoplast carbon metabolism are required for blood-stage parasite survival and organelle maintenance. We found that pyruvate kinase II (PyrKII) is essential for organelle maintenance, but that production of pyruvate by PyrKII is not responsible for this phenomenon. Enzymatic characterization of PyrKII revealed activity against all NDPs and dNDPs tested, suggesting that it may be capable of generating a broad range of nucleotide triphosphates. Conditional mislocalization of PyrKII resulted in decreased transcript levels within the apicoplast that preceded organelle disruption, suggesting that PyrKII is required for organelle maintenance due to its role in nucleotide triphosphate generation.
Data availability
Microarray data have been deposited in GEO under accession code GSE136688.
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Funding
National Institute of Allergy and Infectious Diseases (R01AI065853)
- Sean T Prigge
National Institute of Allergy and Infectious Diseases (R21AI101589)
- Sean T Prigge
National Institute of General Medical Sciences (R25GM109441)
- Cyrianne Keutcha
National Institute of Allergy and Infectious Diseases (T32AI007417)
- Krithika Rajaram
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Swift et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The NTP generating activity of pyruvate kinase II is critical for apicoplast maintenance in plasmodium falciparum
eLife 9:e50807.
https://doi.org/10.7554/eLife.50807
