Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report

Background: Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics profiling has emerged as a promising approach for identifying tuberculosis (TB) biomarkers in urine. This method offers potential in discriminating between samples with varied biological compositions, aiding in the identifi...

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Main Authors: Dr Christoffel Opperman, Dr Marwaan Rylands, Dr Sarishna Singh, Ms Aysha Amien, Mr Yonas Ghebrekristos, Prof Rob Warren, Dr Wynand Goosen
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:International Journal of Infectious Diseases
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971224006969
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author Dr Christoffel Opperman
Dr Marwaan Rylands
Dr Sarishna Singh
Ms Aysha Amien
Mr Yonas Ghebrekristos
Prof Rob Warren
Dr Wynand Goosen
author_facet Dr Christoffel Opperman
Dr Marwaan Rylands
Dr Sarishna Singh
Ms Aysha Amien
Mr Yonas Ghebrekristos
Prof Rob Warren
Dr Wynand Goosen
author_sort Dr Christoffel Opperman
collection DOAJ
description Background: Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics profiling has emerged as a promising approach for identifying tuberculosis (TB) biomarkers in urine. This method offers potential in discriminating between samples with varied biological compositions, aiding in the identification of diagnostic markers for respiratory tract infections. However, direct identification of nontuberculous mycobacteria (NTM) from liquid cultures without subculturing on solid media faces challenges, particularly with existing proteomic diagnostics like matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. Common techniques such as DNA-DNA reverse hybridization (line probe assays) also struggle to discriminate between NTM mixture patterns and have a limited spectrum of NTM that can be identified. Thus, there is a need to characterize NTM metabolic fingerprints in complex liquid broths to facilitate rapid identification without subculturing. Description: Mycobacterium gordonae was cultured at the National Health Laboratory Services Greenpoint TB-laboratory in South Africa, using Löwenstein–Jensen (LJ) media slants. After confirming the species through Sanger sequencing, NTM bacilli were collected, homogenized, and inoculated into Mycobacteria Growth Indicator Tubes (MGIT) containing BD MGIT™ PANTA™ antimicrobial mixture. NMR spectroscopy was conducted at the Department of Chemistry, University of Cape Town, Cape Town, South Africa. Supernatant samples underwent NMR data acquisition using standard Bruker pulse sequences on a Bruker Avance III 600 MHz NMR spectrometer. Discussion: NMR offers low sensitivity initially, but this can be enhanced with higher field strength, cryo- and microprobes, and dynamic nuclear polarization. It provides minimal sample preparation, allows for nondestructive analysis, and exhibits very high reproducibility. NMR can detect all metabolites with an NMR concentration level in one measurement and is suitable for in vivo studies, especially for 1H magnetic resonance spectroscopy. In this regard, NMR could potentially be used to detect the metabolomics profiles of a wide NTM spectrum, including NTM mixtures. To the authors' knowledge, this is the first report that attempts to utilize NMR to identify NTM. The laboratory analysis revealed no significant differences in metabolite quantities between NTM-inoculated and control MGITs. The spectra only displayed broth components, suggesting low analyte concentrations or overshadowing by larger media signals. However, to overcome this, future studies could explore pellet lysate components or vary bacterial concentrations to assess their impact on observed metabolic profiles. Differential precipitation and column chromatography may aid in isolating metabolites from media components. Conclusion: NMR emerges as a compelling choice for NTM identification, offering nondestructive analysis, high reproducibility, and minimal sample preparation, capable of measuring multiple metabolites in a single sample. However, the complexity of MGIT broth media presents challenges for NMR-based NTM identification, necessitating optimization of sample preparation methods. Therefore, in light of the growing demand for improved NTM diagnostic tools, this laboratory case accentuates the need to contemplate innovative approaches with cutting-edge technology for NTM identification.
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spelling doaj-art-3ab0c06b802741eaa51b7d298fcb720b2025-08-20T02:10:57ZengElsevierInternational Journal of Infectious Diseases1201-97122025-03-0115210762110.1016/j.ijid.2024.107621Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case reportDr Christoffel Opperman0Dr Marwaan Rylands1Dr Sarishna Singh2Ms Aysha Amien3Mr Yonas Ghebrekristos4Prof Rob Warren5Dr Wynand Goosen6SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University; National Health Laboratory Service, Green Point TB-Laboratory; Division of Medical Microbiology, Department of Pathology, University of Cape TownDepartment of Chemistry, Faculty of Science, University of Cape TownSAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University; National Health Laboratory Service, Green Point TB-LaboratoryNational Health Laboratory Service, Green Point TB-LaboratorySAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University; National Health Laboratory Service, Green Point TB-LaboratorySAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch UniversitySAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch UniversityBackground: Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics profiling has emerged as a promising approach for identifying tuberculosis (TB) biomarkers in urine. This method offers potential in discriminating between samples with varied biological compositions, aiding in the identification of diagnostic markers for respiratory tract infections. However, direct identification of nontuberculous mycobacteria (NTM) from liquid cultures without subculturing on solid media faces challenges, particularly with existing proteomic diagnostics like matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. Common techniques such as DNA-DNA reverse hybridization (line probe assays) also struggle to discriminate between NTM mixture patterns and have a limited spectrum of NTM that can be identified. Thus, there is a need to characterize NTM metabolic fingerprints in complex liquid broths to facilitate rapid identification without subculturing. Description: Mycobacterium gordonae was cultured at the National Health Laboratory Services Greenpoint TB-laboratory in South Africa, using Löwenstein–Jensen (LJ) media slants. After confirming the species through Sanger sequencing, NTM bacilli were collected, homogenized, and inoculated into Mycobacteria Growth Indicator Tubes (MGIT) containing BD MGIT™ PANTA™ antimicrobial mixture. NMR spectroscopy was conducted at the Department of Chemistry, University of Cape Town, Cape Town, South Africa. Supernatant samples underwent NMR data acquisition using standard Bruker pulse sequences on a Bruker Avance III 600 MHz NMR spectrometer. Discussion: NMR offers low sensitivity initially, but this can be enhanced with higher field strength, cryo- and microprobes, and dynamic nuclear polarization. It provides minimal sample preparation, allows for nondestructive analysis, and exhibits very high reproducibility. NMR can detect all metabolites with an NMR concentration level in one measurement and is suitable for in vivo studies, especially for 1H magnetic resonance spectroscopy. In this regard, NMR could potentially be used to detect the metabolomics profiles of a wide NTM spectrum, including NTM mixtures. To the authors' knowledge, this is the first report that attempts to utilize NMR to identify NTM. The laboratory analysis revealed no significant differences in metabolite quantities between NTM-inoculated and control MGITs. The spectra only displayed broth components, suggesting low analyte concentrations or overshadowing by larger media signals. However, to overcome this, future studies could explore pellet lysate components or vary bacterial concentrations to assess their impact on observed metabolic profiles. Differential precipitation and column chromatography may aid in isolating metabolites from media components. Conclusion: NMR emerges as a compelling choice for NTM identification, offering nondestructive analysis, high reproducibility, and minimal sample preparation, capable of measuring multiple metabolites in a single sample. However, the complexity of MGIT broth media presents challenges for NMR-based NTM identification, necessitating optimization of sample preparation methods. Therefore, in light of the growing demand for improved NTM diagnostic tools, this laboratory case accentuates the need to contemplate innovative approaches with cutting-edge technology for NTM identification.http://www.sciencedirect.com/science/article/pii/S1201971224006969
spellingShingle Dr Christoffel Opperman
Dr Marwaan Rylands
Dr Sarishna Singh
Ms Aysha Amien
Mr Yonas Ghebrekristos
Prof Rob Warren
Dr Wynand Goosen
Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report
International Journal of Infectious Diseases
title Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report
title_full Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report
title_fullStr Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report
title_full_unstemmed Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report
title_short Identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy: A laboratory metabolomics analysis case report
title_sort identifying nontuberculous mycobacteria from a mycobacteria growth indicator tube with nuclear magnetic resonance spectroscopy a laboratory metabolomics analysis case report
url http://www.sciencedirect.com/science/article/pii/S1201971224006969
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