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.
Study ID | ST001279 |
Study Title | K13 mutations driving artemisinin resistance rewrite Plasmodium falciparum’s programmed intra-erythrocytic development and transform mitochondrial physiology |
Study Summary | The 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 Name | Llinás |
First Name | Manuel |
Address | W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA |
mul27@psu.edu | |
Phone | (814) 867-3527 |
Submit Date | 2019-11-18 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2020-06-01 |
Release Version | 1 |
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Collection:
Collection ID: | CO001345 |
Collection Summary: | P. falciparum parasites were cultured at 3% hematocrit in human O+ RBCs (Interstate blood bank, USA) and P. falciparum culture media comprising of RPMI1640 (Thermo Fisher Scientific) supplemented with 0.5% (w/v) Albumax II, 50mg/L hypoxanthine, 0.2% NaHCO3, 25mM HEPES and 10mg/L gentamycin (Fidock et al., 1998). Parasites were cultured at 37ºC in 5% O2, 5%CO2 and 90% N2. For the collection of RNA, proteins and metabolite extracts, parasite cultures at 3% hematocrit and 20 mL or 200 mL volumes were kept in T75 or T225 flasks respectively, with daily media changes. Parasite lines were genotyped by Sanger sequencing for the k13 gene to verify their identities before the start of an experiment. |
Sample Type: | Parasite |