Summary of study ST001652

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 PR001058. The data can be accessed directly via it's Project DOI: 10.21228/M8XX2B 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.

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Study IDST001652
Study TitleAtypical Molecular Basis for Drug Resistance to Mitochondrial AQ: A Function Inhibitors in Plasmodium falciparum
Study SummaryIn this study, we present a clear genotype for the P. falciparum SB1-A6 acridone-resistant clonal parasite strain and, through a combination of targeted and whole-cell methods, establish that the mechanism of resistance to both cytochrome bc1 and DHODH inhibitors results from the contribution of multiple genetic polymorphisms. We find that P. falciparum SB1-A6 accumulates both a copy number variation and a specific mutation in PfDHODH, and both of these genetic polymorphisms contribute to the panresistant phenotype. This study uncovers a mechanism of cross-resistance between PfDHODH and mtETC inhibitors and serves as a cautionary note to future antimalarial combination therapy formulations containing such drugs.
Institute
U.S. Food & Drug Administration
Last NamePainter
First NameHeather
Address10903 New Hampshire Ave., WO 52/72-5324, Silver Spring, MD 20993
EmailHeather.Painter@fda.hhs.gov
Phone240-402-2040
Submit Date2021-01-17
PublicationsDOI:10.1128/AAC.02143-20
Raw Data AvailableYes
Raw Data File Type(s).mzXML
Analysis Type DetailLC-MS
Release Date2021-02-01
Release Version1
Heather Painter Heather Painter
https://dx.doi.org/10.21228/M8XX2B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Collection:

Collection ID:CO001722
Collection Summary:Cells were pelleted and the media aspirated prior to methanol extraction
Sample Type:Plasmodium cells
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