Summary of project PR002643
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 PR002643. The data can be accessed directly via it's Project DOI: 10.21228/M8154F This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002643 |
| Project DOI: | doi: 10.21228/M8154F |
| Project Title: | PfK13-associated artemisinin resistance slows drug activation and enhances antioxidant defence, which can be overcome with sulforaphane |
| Project Summary: | Artemisinin resistance is increasingly prevalent in Africa, raising concerns and highlighting the need to better understand the cellular mechanisms behind this resistance. In Plasmodium falciparum, artemisinin resistance is primarily attributed to mutations in the PfKelch13 (PfK13) gene. In this study, we performed proteomics analysis on a range of artemisinin-resistant (both laboratory-generated and field isolates) and sensitive P. falciparum parasites at 3-6 (hours post invasion) hpi ring- and 22-24 hpi trophozoite-stage, revealing dysregulation of only PfK13 protein abundance. Reduced PfK13 levels were linked to impaired hemoglobin digestion, decreased free heme levels, and consequently, decreased artemisinin activation. Resistant parasites also exhibited elevated thiol levels, indicating a more reduced state. Targeting the parasite redox capacity with sulforaphane potentiated artemisinin activity in vitro and in vivo, offering a potential strategy to overcome resistance. Our findings provide critical insights into the molecular mechanisms of artemisinin resistance and suggest novel therapeutic interventions to restore drug sensitivity. |
| Institute: | Monash University |
| Last Name: | Siddiqui |
| First Name: | Ghizal |
| Address: | 381 Royal Parade, Parkville, Melbourne, Victoria, 3052, Australia |
| Email: | ghizal.siddiqui@monash.edu |
| Phone: | 99039282 |
Summary of all studies in project PR002643
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004194 | PfK13-associated artemisinin resistance slows drug activation and enhances antioxidant defence, which can be overcome with sulforaphane | Plasmodium falciparum | Monash University | MS | 2025-10-06 | 1 | 12 | Uploaded data (1.8G)* |
