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dc.contributor.author | Torres Ortiz, Arturo | |
dc.contributor.author | Coronel, Jorge | |
dc.contributor.author | Vidal, Julia Rios | |
dc.contributor.author | Bonilla, Cesar | |
dc.contributor.author | Moore, David Alexander James | |
dc.contributor.author | Gilman, Robert Hugh | |
dc.contributor.author | Balloux, Francois | |
dc.contributor.author | Kon, Onn Min | |
dc.contributor.author | Didelot, Xavier | |
dc.contributor.author | Grandjean, Louis | |
dc.date.accessioned | 2022-02-01T21:18:29Z | |
dc.date.available | 2022-02-01T21:18:29Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12866/11322 | |
dc.description.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 | en_US |
dc.language.iso | eng | |
dc.publisher | Springer Nature | |
dc.relation.ispartofseries | Nature Communications | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es | |
dc.subject | Antimicrobial resistance | en_US |
dc.subject | Bacterial genetics | en_US |
dc.subject | Genome-wide association studies | en_US |
dc.subject | Phylogenetics | en_US |
dc.subject | Tuberculosis | en_US |
dc.title | Genomic signatures of pre-resistance in Mycobacterium tuberculosis. | en_US |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | https://doi.org/10.1038/s41467-021-27616-7 | |
dc.relation.issn | 2041-1723 |
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