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 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN002120 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 |
| Column | Phenomenex Synergi Hydro RP 100 A (100 x 2mm,2.5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Exactive Plus Orbitrap |
| Ion Mode | NEGATIVE |
| Units | Peak Area |
MS:
| MS ID: | MS001975 |
| Analysis ID: | AN002120 |
| Instrument Name: | Thermo Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Raw data files from the Thermo Exactive Plus orbitrap (.raw) were converted to a format compatible with our analysis software (.raw¡.mzXML) and spectral data (.mzXML files) were visualized in MAVEN. The labeled [13C4, 15N1]-Aspartate internal standard intensity was assessed for technical reproducibility. Peaks for each metabolite in the targeted library were identified based on proximity to standard retention time, the observed mass falling within 10 ppm of the expected m/z (calculated from the monoisotopic mass), and the signal/blank ratio (minimum, 10,000 ions). Based upon the above criteria, peaks were manually inspected and demarcated as good or bad based on peak shape. Peak areas were exported into an R working environment (http://www.R-project.org) to calculate log2 fold changes for each sample compared to an untreated control. Metabolites that were not reliably detected across 90% of all the trials were removed prior to additional analysis to minimize subsequent imputation bias. The peak areas for any remaining metabolites not detected were imputed to have 10,000 ions, and metabolites detected below background levels (negative after blank subtraction) were maintained as “0” prior to averaging and log2 calculation. Because our extraction method did not include a wash step we excluded metabolites found in the RPMI-based medium. |
| Ion Mode: | NEGATIVE |
