The Cryptic, Consortium;
(2024)
Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach.
Nature Communications
, 15
, Article 488. 10.1038/s41467-023-44325-5.
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Abstract
The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, we used a multivariable linear mixed model alongside whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms.
| Type: | Article |
|---|---|
| Title: | Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-023-44325-5 |
| Publisher version: | https://doi.org/10.1038/s41467-023-44325-5 |
| Language: | English |
| Additional information: | © 2024 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Antibiotics, Antimicrobial resistance, Bacterial genes, Infectious-disease diagnostics, Pathogens |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10185862 |
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