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Genomic signatures of pre-resistance in Mycobacterium tuberculosis.

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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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