Summary of Study ST001279

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000864. The data can be accessed directly via it's Project DOI: 10.21228/M80T2X This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001279
Study TitleK13 mutations driving artemisinin resistance rewrite Plasmodium falciparum’s programmed intra-erythrocytic development and transform mitochondrial physiology
Study SummaryThe emergence of artemisinin resistance in Southeast Asia, dictated by mutations in the Plasmodium falciparum k13 gene, has compromised antimalarial efficacy and created a core vulnerability in the global malaria elimination campaign. Applying quantitative transcriptomics, proteomics, and metabolomics to a panel of isogenic K13 mutant or wild-type P. falciparum lines, we observe that K13 mutations reprogram multiple aspects of intra-erythrocytic parasite biology. These changes impact its cell cycle periodicity, the unfolded protein response and protein degradation, vesicular trafficking and endocytosis, and mitochondrial functions including the TCA cycle, the electron transport chain, and redox regulation. Ring-stage artemisinin resistance mediated by the K13 R539T mutation was neutralized using atovaquone, an electron transport chain inhibitor. Our data suggest that modification of mitochondrial physiology, accompanied by other processes to reduce artemisinin’s proteotoxic effects, help protect parasites against this pro-oxidant drug, allowing resumption of growth once the rapidly-cleared artemisinins have reached sub-therapeutic levels.
Institute
Pennsylvania State University
Last NameLlinás
First NameManuel
AddressW126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA
Emailmul27@psu.edu
Phone(814) 867-3527
Submit Date2019-11-18
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2020-06-01
Release Version1
Manuel Llinás Manuel Llinás
https://dx.doi.org/10.21228/M80T2X
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Treatment:

Treatment ID:TR001366
Treatment Summary:Mycoplasma-free Cam3.IIC580Y and Cam3.IIWT parasites were doubly synchronized by 5% D-Sorbitol in each generation for at least two generations. 0-3 hpi early rings of each parasite line were treated for 3h at 350 nM or 70 nM DHA along with vehicle-treated 0.05% DMSO controls in two to three independent experiments. 24 hpi trophozoites were similarly treated with DHA or DMSO control in a single experiment for each parasite line and subsequently magnetically enriched using MACS CS columns on the SuperMACS™ II Separator (Miltenyi Biotec, Inc.) to remove uninfected RBCs.
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