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Title
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Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach
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Author
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Institution/Organisation
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CRyPTIC Consortium
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Nature communications
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Publication
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2024
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ISSN
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2041-1723
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DOI
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10.1038/S41467-023-44325-5
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Volume/pages
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15
:1
(2024)
, p. 1-13
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Article Reference
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488
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ISI
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001142873900014
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Pubmed ID
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38216576
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Full text (Publisher's DOI)
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Full text (open access)
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