Summary of project PR000864
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
| Project ID: | PR000864 |
| Project DOI: | doi: 10.21228/M80T2X |
| Project Title: | K13 mutations driving artemisinin resistance rewrite Plasmodium falciparum’s programmed intra-erythrocytic development and transform mitochondrial physiology |
| Project 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 |
| Email: | mul27@psu.edu |
| Phone: | (814) 867-3527 |
Summary of all studies in project PR000864
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001279 | K13 mutations driving artemisinin resistance rewrite Plasmodium falciparum’s programmed intra-erythrocytic development and transform mitochondrial physiology | Plasmodium falciparum | Pennsylvania State University | MS | 2020-06-01 | 1 | 63 | Uploaded data (15.2G)* |
