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 |
|