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The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot
Multidrug-resistant tuberculosis (MDR-TB) is among the most frequent causes of death due to antimicrobial resistance. Although only 3% of global TB cases are MDR, geographical hotspots with up to 40% of MDR-TB have been observed in countries of the former Soviet Union. While the quality of TB contro...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10082831/ https://www.ncbi.nlm.nih.gov/pubmed/37031225 http://dx.doi.org/10.1038/s41467-023-37719-y |
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author | Loiseau, Chloé Windels, Etthel M. Gygli, Sebastian M. Jugheli, Levan Maghradze, Nino Brites, Daniela Ross, Amanda Goig, Galo Reinhard, Miriam Borrell, Sonia Trauner, Andrej Dötsch, Anna Aspindzelashvili, Rusudan Denes, Rebecca Reither, Klaus Beisel, Christian Tukvadze, Nestani Avaliani, Zaza Stadler, Tanja Gagneux, Sebastien |
author_facet | Loiseau, Chloé Windels, Etthel M. Gygli, Sebastian M. Jugheli, Levan Maghradze, Nino Brites, Daniela Ross, Amanda Goig, Galo Reinhard, Miriam Borrell, Sonia Trauner, Andrej Dötsch, Anna Aspindzelashvili, Rusudan Denes, Rebecca Reither, Klaus Beisel, Christian Tukvadze, Nestani Avaliani, Zaza Stadler, Tanja Gagneux, Sebastien |
author_sort | Loiseau, Chloé |
collection | PubMed |
description | Multidrug-resistant tuberculosis (MDR-TB) is among the most frequent causes of death due to antimicrobial resistance. Although only 3% of global TB cases are MDR, geographical hotspots with up to 40% of MDR-TB have been observed in countries of the former Soviet Union. While the quality of TB control and patient-related factors are known contributors to such hotspots, the role of the pathogen remains unclear. Here we show that in the country of Georgia, a known hotspot of MDR-TB, MDR Mycobacterium tuberculosis strains of lineage 4 (L4) transmit less than their drug-susceptible counterparts, whereas most MDR strains of L2 suffer no such defect. Our findings further indicate that the high transmission fitness of these L2 strains results from epistatic interactions between the rifampicin resistance-conferring mutation RpoB S450L, compensatory mutations in the RNA polymerase, and other pre-existing genetic features of L2/Beijing clones that circulate in Georgia. We conclude that the transmission fitness of MDR M. tuberculosis strains is heterogeneous, but can be as high as drug-susceptible forms, and that such highly drug-resistant and transmissible strains contribute to the emergence and maintenance of hotspots of MDR-TB. As these strains successfully overcome the metabolic burden of drug resistance, and given the ongoing rollout of new treatment regimens against MDR-TB, proper surveillance should be implemented to prevent these strains from acquiring resistance to the additional drugs. |
format | Online Article Text |
id | pubmed-10082831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100828312023-04-10 The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot Loiseau, Chloé Windels, Etthel M. Gygli, Sebastian M. Jugheli, Levan Maghradze, Nino Brites, Daniela Ross, Amanda Goig, Galo Reinhard, Miriam Borrell, Sonia Trauner, Andrej Dötsch, Anna Aspindzelashvili, Rusudan Denes, Rebecca Reither, Klaus Beisel, Christian Tukvadze, Nestani Avaliani, Zaza Stadler, Tanja Gagneux, Sebastien Nat Commun Article Multidrug-resistant tuberculosis (MDR-TB) is among the most frequent causes of death due to antimicrobial resistance. Although only 3% of global TB cases are MDR, geographical hotspots with up to 40% of MDR-TB have been observed in countries of the former Soviet Union. While the quality of TB control and patient-related factors are known contributors to such hotspots, the role of the pathogen remains unclear. Here we show that in the country of Georgia, a known hotspot of MDR-TB, MDR Mycobacterium tuberculosis strains of lineage 4 (L4) transmit less than their drug-susceptible counterparts, whereas most MDR strains of L2 suffer no such defect. Our findings further indicate that the high transmission fitness of these L2 strains results from epistatic interactions between the rifampicin resistance-conferring mutation RpoB S450L, compensatory mutations in the RNA polymerase, and other pre-existing genetic features of L2/Beijing clones that circulate in Georgia. We conclude that the transmission fitness of MDR M. tuberculosis strains is heterogeneous, but can be as high as drug-susceptible forms, and that such highly drug-resistant and transmissible strains contribute to the emergence and maintenance of hotspots of MDR-TB. As these strains successfully overcome the metabolic burden of drug resistance, and given the ongoing rollout of new treatment regimens against MDR-TB, proper surveillance should be implemented to prevent these strains from acquiring resistance to the additional drugs. Nature Publishing Group UK 2023-04-08 /pmc/articles/PMC10082831/ /pubmed/37031225 http://dx.doi.org/10.1038/s41467-023-37719-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Loiseau, Chloé Windels, Etthel M. Gygli, Sebastian M. Jugheli, Levan Maghradze, Nino Brites, Daniela Ross, Amanda Goig, Galo Reinhard, Miriam Borrell, Sonia Trauner, Andrej Dötsch, Anna Aspindzelashvili, Rusudan Denes, Rebecca Reither, Klaus Beisel, Christian Tukvadze, Nestani Avaliani, Zaza Stadler, Tanja Gagneux, Sebastien The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot |
title | The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot |
title_full | The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot |
title_fullStr | The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot |
title_full_unstemmed | The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot |
title_short | The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot |
title_sort | relative transmission fitness of multidrug-resistant mycobacterium tuberculosis in a drug resistance hotspot |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10082831/ https://www.ncbi.nlm.nih.gov/pubmed/37031225 http://dx.doi.org/10.1038/s41467-023-37719-y |
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