Summary of project PR001058

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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

Summary of all studies in project PR001058

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : 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)*