Summary of project PR001058

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

Project ID: PR001058
Project DOI:doi: 10.21228/M8XX2B
Project Title:Atypical Molecular Basis for Drug Resistance to Mitochondrial Function Inhibitors in AQ: A Plasmodium falciparum
Project Summary:In 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 Name:Painter
First Name:Heather
Address:10903 New Hampshire Ave., WO 52/72-5324, Silver Spring, MD 20993
Email:Heather.Painter@fda.hhs.gov
Phone:240-402-2040

Summary of all studies in project PR001058

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)		 Release
Date		VersionSamplesDownload
(* : Contains raw data)
ST001652 Atypical Molecular Basis for Drug Resistance to Mitochondrial AQ: A Function Inhibitors in Plasmodium falciparum Plasmodium falciparum U.S. Food & Drug Administration MS 2021-02-01 1 17 Uploaded data (123.4M)*
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