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Genomic signatures of pre-resistance in Mycobacterium tuberculosis
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Torres Ortiz, Arturo, Coronel, Jorge, Vidal, Julia Rios, Bonilla, Cesar, Moore, David A. J., Gilman, Robert H., Balloux, Francois, Kon, Onn Min, Didelot, Xavier and Grandjean, Louis (2021) Genomic signatures of pre-resistance in Mycobacterium tuberculosis. Nature Communications, 12 (1). 7312. doi:10.1038/s41467-021-27616-7 ISSN 2041-1723.
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Official URL: https://doi.org/10.1038/s41467-021-27616-7
Abstract
Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||
SWORD Depositor: | Library Publications Router | ||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Mycobacterium tuberculosis, Tuberculosis -- Genetic aspects, Genomics, Drug resistance in microorganisms—Genetic aspects, Multidrug-resistant tuberculosis | ||||||||||||||||||
Journal or Publication Title: | Nature Communications | ||||||||||||||||||
Publisher: | Nature Publishing Group UK | ||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||
Official Date: | 15 December 2021 | ||||||||||||||||||
Dates: |
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Volume: | 12 | ||||||||||||||||||
Number: | 1 | ||||||||||||||||||
Article Number: | 7312 | ||||||||||||||||||
DOI: | 10.1038/s41467-021-27616-7 | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Reuse Statement (publisher, data, author rights): | ** From Springer Nature via Jisc Publications Router ** History: received 18-05-2021; accepted 29-11-2021; collection 12-2021; registration 02-12-2021; pub-electronic 15-12-2021; online 15-12-2021. ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 20 December 2021 | ||||||||||||||||||
Date of first compliant Open Access: | 22 December 2021 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
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