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.
| Study ID | ST001652 |
| Study Title | Atypical Molecular Basis for Drug Resistance to Mitochondrial AQ: A Function Inhibitors in Plasmodium falciparum |
| Study 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 |
| Heather.Painter@fda.hhs.gov | |
| Phone | 240-402-2040 |
| Submit Date | 2021-01-17 |
| Publications | DOI:10.1128/AAC.02143-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-02-01 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Factors:
Subject type: Cultured cells; Subject species: Plasmodium falciparum (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment |
|---|---|---|---|
| SA151731 | 9_A6_AT1 | Drug Resistant | Atovaquone |
| SA151732 | 19_A6_AT2 | Drug Resistant | Atovaquone |
| SA151733 | 28_A6_AT3 | Drug Resistant | Atovaquone |
| SA151734 | 31_A6_CT3 | Drug Resistant | Control |
| SA151735 | 21_A6_CT2 | Drug Resistant | Control |
| SA151736 | 7_A6_CT1 | Drug Resistant | Control |
| SA151737 | 8_A6_DT1 | Drug Resistant | DSM-1 |
| SA151738 | 20_A6_DT2 | Drug Resistant | DSM-1 |
| SA151739 | 26_A6_DT3 | Drug Resistant | DSM-1 |
| SA151740 | 17_D6_DT2 | Drug Resistant | DSM-1 |
| SA151741 | 12_D6_AT1 | Wild-type | Atovaquone |
| SA151742 | 16_D6_AT2 | Wild-type | Atovaquone |
| SA151743 | 25_D6_AT3 | Wild-type | Atovaquone |
| SA151744 | 10_D6_CT1 | Wild-type | Control |
| SA151745 | 29_D6_CT3 | Wild-type | Control |
| SA151746 | 18_D6_CT2 | Wild-type | Control |
| SA151747 | 11_D6_DT1 | Wild-type | DSM-1 |
| Showing results 1 to 17 of 17 |
