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Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis

The detection of pre-extensively (pre-XDR) and extensively drug-resistant tuberculosis (XDR-TB) is challenging. Drug-susceptibility tests for some anti-TB drugs, especially ethambutol (ETH) and ethionamide (ETO), are problematic due to overlapping thresholds to differentiate between susceptible and...

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Autores principales: Chaiyachat, Pratchakan, Kaewseekhao, Benjawan, Chaiprasert, Angkana, Kamolwat, Phalin, Nonghanphithak, Ditthawat, Phetcharaburanin, Jutarop, Sirichoat, Auttawit, Ong, Rick Twee-Hee, Faksri, Kiatichai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224971/
https://www.ncbi.nlm.nih.gov/pubmed/37244948
http://dx.doi.org/10.1038/s41598-023-35882-2
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author Chaiyachat, Pratchakan
Kaewseekhao, Benjawan
Chaiprasert, Angkana
Kamolwat, Phalin
Nonghanphithak, Ditthawat
Phetcharaburanin, Jutarop
Sirichoat, Auttawit
Ong, Rick Twee-Hee
Faksri, Kiatichai
author_facet Chaiyachat, Pratchakan
Kaewseekhao, Benjawan
Chaiprasert, Angkana
Kamolwat, Phalin
Nonghanphithak, Ditthawat
Phetcharaburanin, Jutarop
Sirichoat, Auttawit
Ong, Rick Twee-Hee
Faksri, Kiatichai
author_sort Chaiyachat, Pratchakan
collection PubMed
description The detection of pre-extensively (pre-XDR) and extensively drug-resistant tuberculosis (XDR-TB) is challenging. Drug-susceptibility tests for some anti-TB drugs, especially ethambutol (ETH) and ethionamide (ETO), are problematic due to overlapping thresholds to differentiate between susceptible and resistant phenotypes. We aimed to identify possible metabolomic markers to detect Mycobacterium tuberculosis (Mtb) strains causing pre-XDR and XDR-TB. The metabolic patterns of ETH- and ETO-resistant Mtb isolates were also investigated. Metabolomics of 150 Mtb isolates (54 pre-XDR, 63 XDR-TB and 33 pan-susceptible; pan-S) were investigated. Metabolomics of ETH and ETO phenotypically resistant subgroups were analyzed using UHPLC-ESI-QTOF-MS/MS. Orthogonal partial least-squares discriminant analysis revealed distinct separation in all pairwise comparisons among groups. Two metabolites (meso-hydroxyheme and itaconic anhydride) were able to differentiate the pre-XDR and XDR-TB groups from the pan-S group with 100% sensitivity and 100% specificity. In comparisons of the ETH and ETO phenotypically resistant subsets, sets of increased (ETH = 15, ETO = 7) and decreased (ETH = 1, ETO = 6) metabolites specific for the resistance phenotype of each drug were found. We demonstrated the potential for metabolomics of Mtb to differentiate among types of DR-TB as well as between isolates that were phenotypically resistant to ETO and ETH. Thus, metabolomics might be further applied for DR-TB diagnosis and patient management.
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spelling pubmed-102249712023-05-29 Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis Chaiyachat, Pratchakan Kaewseekhao, Benjawan Chaiprasert, Angkana Kamolwat, Phalin Nonghanphithak, Ditthawat Phetcharaburanin, Jutarop Sirichoat, Auttawit Ong, Rick Twee-Hee Faksri, Kiatichai Sci Rep Article The detection of pre-extensively (pre-XDR) and extensively drug-resistant tuberculosis (XDR-TB) is challenging. Drug-susceptibility tests for some anti-TB drugs, especially ethambutol (ETH) and ethionamide (ETO), are problematic due to overlapping thresholds to differentiate between susceptible and resistant phenotypes. We aimed to identify possible metabolomic markers to detect Mycobacterium tuberculosis (Mtb) strains causing pre-XDR and XDR-TB. The metabolic patterns of ETH- and ETO-resistant Mtb isolates were also investigated. Metabolomics of 150 Mtb isolates (54 pre-XDR, 63 XDR-TB and 33 pan-susceptible; pan-S) were investigated. Metabolomics of ETH and ETO phenotypically resistant subgroups were analyzed using UHPLC-ESI-QTOF-MS/MS. Orthogonal partial least-squares discriminant analysis revealed distinct separation in all pairwise comparisons among groups. Two metabolites (meso-hydroxyheme and itaconic anhydride) were able to differentiate the pre-XDR and XDR-TB groups from the pan-S group with 100% sensitivity and 100% specificity. In comparisons of the ETH and ETO phenotypically resistant subsets, sets of increased (ETH = 15, ETO = 7) and decreased (ETH = 1, ETO = 6) metabolites specific for the resistance phenotype of each drug were found. We demonstrated the potential for metabolomics of Mtb to differentiate among types of DR-TB as well as between isolates that were phenotypically resistant to ETO and ETH. Thus, metabolomics might be further applied for DR-TB diagnosis and patient management. Nature Publishing Group UK 2023-05-27 /pmc/articles/PMC10224971/ /pubmed/37244948 http://dx.doi.org/10.1038/s41598-023-35882-2 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 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/) .
spellingShingle Article
Chaiyachat, Pratchakan
Kaewseekhao, Benjawan
Chaiprasert, Angkana
Kamolwat, Phalin
Nonghanphithak, Ditthawat
Phetcharaburanin, Jutarop
Sirichoat, Auttawit
Ong, Rick Twee-Hee
Faksri, Kiatichai
Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
title Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
title_full Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
title_fullStr Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
title_full_unstemmed Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
title_short Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
title_sort metabolomic analysis of mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224971/
https://www.ncbi.nlm.nih.gov/pubmed/37244948
http://dx.doi.org/10.1038/s41598-023-35882-2
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