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Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

BACKGROUND: Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistan...

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Autores principales: Morey-León, Gabriel, Andrade-Molina, Derly, Fernández-Cadena, Juan Carlos, Berná, Luisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769008/
https://www.ncbi.nlm.nih.gov/pubmed/36544084
http://dx.doi.org/10.1186/s12864-022-09042-1
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author Morey-León, Gabriel
Andrade-Molina, Derly
Fernández-Cadena, Juan Carlos
Berná, Luisa
author_facet Morey-León, Gabriel
Andrade-Molina, Derly
Fernández-Cadena, Juan Carlos
Berná, Luisa
author_sort Morey-León, Gabriel
collection PubMed
description BACKGROUND: Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. RESULTS: Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. CONCLUSION: This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09042-1.
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spelling pubmed-97690082022-12-22 Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador Morey-León, Gabriel Andrade-Molina, Derly Fernández-Cadena, Juan Carlos Berná, Luisa BMC Genomics Research BACKGROUND: Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. RESULTS: Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. CONCLUSION: This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09042-1. BioMed Central 2022-12-21 /pmc/articles/PMC9769008/ /pubmed/36544084 http://dx.doi.org/10.1186/s12864-022-09042-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Morey-León, Gabriel
Andrade-Molina, Derly
Fernández-Cadena, Juan Carlos
Berná, Luisa
Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador
title Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador
title_full Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador
title_fullStr Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador
title_full_unstemmed Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador
title_short Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador
title_sort comparative genomics of drug-resistant strains of mycobacterium tuberculosis in ecuador
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769008/
https://www.ncbi.nlm.nih.gov/pubmed/36544084
http://dx.doi.org/10.1186/s12864-022-09042-1
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