Summary of Study ST002181
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 PR001388. The data can be accessed directly via it's Project DOI: 10.21228/M89H7H 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 | ST002181 |
Study Title | Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages. |
Study Summary | The emergence of multidrug resistance in Plasmodium falciparum parasites presents a significant obstacle to the malaria elimination agenda. Resistance to piperaquine (PPQ), an important first-line partner drug, has spread across Southeast Asia where it has contributed to widespread treatment failures. The genetic cause of resistance to PPQ is attributable to a novel set of amino acid substitutions in the P. falciparum chloroquine resistance transporter (PfCRT). In this study, we used magnetically-purified trophozoite extracts from seven different lines comprising five genetically-modified and two field isolates. Three independent extractions with triplicate technical repeats were run by mass spectrometry on positive and negative modes and spectral peak raw data analyzed to obtain the fold change difference between the samples and parental control, Dd2Dd2crt. We show that PPQ-resistant, PfCRT mutant asexual blood stage parasites accumulate higher levels of hemoglobin-derived peptides than do their PPQ-sensitive counterparts. |
Institute | Pennsylvania State University |
Department | Department of Biochemistry and Molecular Biology |
Last Name | Llinas |
First Name | Manuel |
Address | W126 Millenium Science Complex, University Park, PA 16802 |
manuel@psu.edu | |
Phone | 814-867-3527 |
Submit Date | 2022-05-18 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2022-10-19 |
Release Version | 1 |
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Collection:
Collection ID: | CO002260 |
Collection Summary: | Mycoplasma-free parasites were sorbitol-synchronized in each generation for at least two generations followed by magnetic enrichment of 32 hr post-invasion trophozoites using MACS CS columns on a SuperMACS™ II Separator (Miltenyi Biotec, Inc.) to remove uninfected RBCs. Trophozoite counts were determined on a hemocytometer. Parasites were lysed in 1 mL of 90% cold methanol, containing 0.5 μM of the internal standard [13C4, 15N1]-Aspartate (Cambridge Isotope) to correct for technical variations arising from sample processing. Samples were vortexed to disrupt cell pellets and to generate uniform homogenates, which were centrifuged (13,000´ g for 10 min) and the supernatants then harvested. Supernatants were dried under nitrogen prior to resuspension in HPLC-grade water for LC-MS analysis. |
Sample Type: | Plasmodium cells |