A Global Survey of ATPase Activity in Plasmodium falciparum Asexual Blood Stages and Gametocytes

Ortega, Corrie; Frando, Andrew; Webb-Robertson, Bobbie-Jo; Anderson, Lindsey N.; Fleck, Neil; Flannery, Erika L.; Fishbaugher, Matthew; Murphree, Taylor A.; Hansen, Joshua R.; Smith, Richard D.; Kappe, Stefan H.  I.; Wright, Aaron T.; Grundner, Christoph

doi:10.1074/mcp.RA117.000088

A Global Survey of ATPase Activity in Plasmodium falciparum Asexual Blood Stages and Gametocytes

Journal Article · Fri Oct 27 04:00:00 EDT 2017 · Molecular and Cellular Proteomics

DOI:https://doi.org/10.1074/mcp.RA117.000088· OSTI ID:1422286

Ortega, Corrie; Frando, Andrew; Webb-Robertson, Bobbie-Jo; Anderson, Lindsey N.; Fleck, Neil; Flannery, Erika L.; Fishbaugher, Matthew; Murphree, Taylor A.; Hansen, Joshua R.; Smith, Richard D.; Kappe, Stefan H. I.; Wright, Aaron T.; Grundner, Christoph

Effective malaria control and elimination in hyperendemic areas of the world will require treatment of disease-causing Plasmodium falciparum (Pf) blood stage infection but also blocking parasite transmission from humans to mosquito to prevent disease spread. Numerous antimalarial drugs have become ineffective due to parasite drug resistance and many currently used therapies do not kill gametocytes, highly specialized sexual parasite stages with distinct physiology that are necessary for transmission from the human host to the mosquito vector. Further confounding next generation drug development against Pf is the lack of known biochemical activity for most parasite gene products as well as the unknown metabolic needs of non-replicating gametocyte. Here, we take a systematic activity-based proteomics approach to survey the large and druggable ATPase family that is associated with replicating blood stage asexual parasites and transmissible gametocytes. We experimentally confirm existing annotation and predict ATPase function for 38 uncharacterized proteins. ATPase activity broadly changes during the transition from asexual schizonts to gametocytes, indicating altered metabolism and regulatory roles of ATPases specific for each lifecycle stage. By mapping the activity of ATPases associated with gametocytogenesis, we assign biochemical activity to a large number of uncharacterized proteins and identify new candidate transmission blocking targets.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1422286

Report Number(s):: PNNL-SA-121236; 24698; 49531; 453040220

Journal Information:: Molecular and Cellular Proteomics, Journal Name: Molecular and Cellular Proteomics Journal Issue: 1 Vol. 17; ISSN 1535-9476

Publisher:: American Society for Biochemistry and Molecular Biology

Country of Publication:: United States

Language:: English

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