Taxonomic group: bacteria / Actinobacteria (Phylum: Actinobacteria)
Associated disease: infection due to Mycobacterium tuberculosis [ICD11: XN1N2 ]
 
NCBI PubMed ID: 26038762
Publication DOI: 10.1038/emi.2015.6
Journal NLM ID: 101594885
Publisher: Philadelphia, PA: Taylor & Francis
Correspondence: Lau SK <skplauhkucc.hku.hk>; Woo PC <pcywoohkucc.hku.hk>
Institutions: State Key Laboratory of Emerging Infectious Diseases, Hong Kong, China, Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China, Department of Microbiology, The University of Hong Kong, Hong Kong, China, Department of Pathology, The University of Hong Kong, Hong Kong, China

Although previous studies have reported the use of metabolomics for Mycobacterium species differentiation, little is known about the potential of extracellular metabolites of Mycobacterium tuberculosis (MTB) as specific biomarkers. Using an optimized ultrahigh performance liquid chromatography-electrospray ionization-quadruple time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) platform, we characterized the extracellular metabolomes of culture supernatant of nine MTB strains and nine non-tuberculous Mycobacterium (NTM) strains (four M. avium complex, one M. bovis Bacillus Calmette-Guérin (BCG), one M. chelonae, one M. fortuitum and two M. kansasii). Principal component analysis readily distinguished the metabolomes between MTB and NTM. Using multivariate and univariate analysis, 24 metabolites with significantly higher levels in MTB were identified. While seven metabolites were identified by tandem mass spectrometry (MS/MS), the other 17 metabolites were unidentified by MS/MS against database matching, suggesting that they may be potentially novel compounds. One metabolite was identified as dexpanthenol, the alcohol analog of pantothenic acid (vitamin B5), which was not known to be produced by bacteria previously. Four metabolites were identified as 1-tuberculosinyladenosine (1-TbAd), a product of the virulence-associated enzyme Rv3378c, and three previously undescribed derivatives of 1-TbAd. Two derivatives differ from 1-TbAd by the ribose group of the nucleoside while the other likely differs by the base. The remaining two metabolites were identified as a tetrapeptide, Val-His-Glu-His, and a monoacylglycerophosphoglycerol, phosphatidylglycerol (PG) (16:0/0:0), respectively. Further studies on the chemical structure and biosynthetic pathway of these MTB-specific metabolites would help understand their biological functions. Studies on clinical samples from tuberculosis patients are required to explore for their potential role as diagnostic biomarkers

specific, Mycobacterium tuberculosis, metabolomics, diagnosis, biomarkers

Structure type: monomer ; 540.3557 [M]+
C₃₀H₄₆N₅O₄
Location inside paper: Fig. 5, A
Compound class: nucleoside
Contained glycoepitopes: IEDB_149136
 
Methods: MS/MS, LC-MS, ESI-QTOF-MS, cell growth, sonication, centrifugation, ion chromatography, UHPLC, PCA, PLS-DA
 
Related record ID(s): 49307, 49308, 49309
NCBI Taxonomy refs (TaxIDs): 83332, 1773
Show glycosyltransferases
 

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Taxonomic group: bacteria / Actinobacteria (Phylum: Actinobacteria)
Associated disease: infection due to Mycobacterium tuberculosis [ICD11: XN1N2 ]
 
NCBI PubMed ID: 26038762
Publication DOI: 10.1038/emi.2015.6
Journal NLM ID: 101594885
Publisher: Philadelphia, PA: Taylor & Francis
Correspondence: Lau SK <skplauhkucc.hku.hk>; Woo PC <pcywoohkucc.hku.hk>
Institutions: State Key Laboratory of Emerging Infectious Diseases, Hong Kong, China, Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China, Department of Microbiology, The University of Hong Kong, Hong Kong, China, Department of Pathology, The University of Hong Kong, Hong Kong, China

Although previous studies have reported the use of metabolomics for Mycobacterium species differentiation, little is known about the potential of extracellular metabolites of Mycobacterium tuberculosis (MTB) as specific biomarkers. Using an optimized ultrahigh performance liquid chromatography-electrospray ionization-quadruple time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) platform, we characterized the extracellular metabolomes of culture supernatant of nine MTB strains and nine non-tuberculous Mycobacterium (NTM) strains (four M. avium complex, one M. bovis Bacillus Calmette-Guérin (BCG), one M. chelonae, one M. fortuitum and two M. kansasii). Principal component analysis readily distinguished the metabolomes between MTB and NTM. Using multivariate and univariate analysis, 24 metabolites with significantly higher levels in MTB were identified. While seven metabolites were identified by tandem mass spectrometry (MS/MS), the other 17 metabolites were unidentified by MS/MS against database matching, suggesting that they may be potentially novel compounds. One metabolite was identified as dexpanthenol, the alcohol analog of pantothenic acid (vitamin B5), which was not known to be produced by bacteria previously. Four metabolites were identified as 1-tuberculosinyladenosine (1-TbAd), a product of the virulence-associated enzyme Rv3378c, and three previously undescribed derivatives of 1-TbAd. Two derivatives differ from 1-TbAd by the ribose group of the nucleoside while the other likely differs by the base. The remaining two metabolites were identified as a tetrapeptide, Val-His-Glu-His, and a monoacylglycerophosphoglycerol, phosphatidylglycerol (PG) (16:0/0:0), respectively. Further studies on the chemical structure and biosynthetic pathway of these MTB-specific metabolites would help understand their biological functions. Studies on clinical samples from tuberculosis patients are required to explore for their potential role as diagnostic biomarkers

specific, Mycobacterium tuberculosis, metabolomics, diagnosis, biomarkers

Structure type: monomer ; 524.3609 [M]+
C₃₀H₄₆N₅O₃
Location inside paper: Fig. 5, B
Compound class: nucleoside
 
Methods: MS/MS, LC-MS, ESI-QTOF-MS, cell growth, sonication, centrifugation, ion chromatography, UHPLC, PCA, PLS-DA
 
Related record ID(s): 49306, 49308, 49309
NCBI Taxonomy refs (TaxIDs): 83332, 1773
Show glycosyltransferases
 

Convert structure to SMILES & 3D GlycoCT β-test WURCS 2.0 GLYCAM GlycoCT (external) GlycoCT XML (ext) GlydeII XML LinUCS Fragmentize Mol. weight

Simulate NMR spectra (GODDESS)

Show Sweet-II 3D model Generate 3D coords by GLYCAM

Taxonomic group: bacteria / Actinobacteria (Phylum: Actinobacteria)
Associated disease: infection due to Mycobacterium tuberculosis [ICD11: XN1N2 ]
 
NCBI PubMed ID: 26038762
Publication DOI: 10.1038/emi.2015.6
Journal NLM ID: 101594885
Publisher: Philadelphia, PA: Taylor & Francis
Correspondence: Lau SK <skplauhkucc.hku.hk>; Woo PC <pcywoohkucc.hku.hk>
Institutions: State Key Laboratory of Emerging Infectious Diseases, Hong Kong, China, Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China, Department of Microbiology, The University of Hong Kong, Hong Kong, China, Department of Pathology, The University of Hong Kong, Hong Kong, China

Although previous studies have reported the use of metabolomics for Mycobacterium species differentiation, little is known about the potential of extracellular metabolites of Mycobacterium tuberculosis (MTB) as specific biomarkers. Using an optimized ultrahigh performance liquid chromatography-electrospray ionization-quadruple time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) platform, we characterized the extracellular metabolomes of culture supernatant of nine MTB strains and nine non-tuberculous Mycobacterium (NTM) strains (four M. avium complex, one M. bovis Bacillus Calmette-Guérin (BCG), one M. chelonae, one M. fortuitum and two M. kansasii). Principal component analysis readily distinguished the metabolomes between MTB and NTM. Using multivariate and univariate analysis, 24 metabolites with significantly higher levels in MTB were identified. While seven metabolites were identified by tandem mass spectrometry (MS/MS), the other 17 metabolites were unidentified by MS/MS against database matching, suggesting that they may be potentially novel compounds. One metabolite was identified as dexpanthenol, the alcohol analog of pantothenic acid (vitamin B5), which was not known to be produced by bacteria previously. Four metabolites were identified as 1-tuberculosinyladenosine (1-TbAd), a product of the virulence-associated enzyme Rv3378c, and three previously undescribed derivatives of 1-TbAd. Two derivatives differ from 1-TbAd by the ribose group of the nucleoside while the other likely differs by the base. The remaining two metabolites were identified as a tetrapeptide, Val-His-Glu-His, and a monoacylglycerophosphoglycerol, phosphatidylglycerol (PG) (16:0/0:0), respectively. Further studies on the chemical structure and biosynthetic pathway of these MTB-specific metabolites would help understand their biological functions. Studies on clinical samples from tuberculosis patients are required to explore for their potential role as diagnostic biomarkers

specific, Mycobacterium tuberculosis, metabolomics, diagnosis, biomarkers

Structure type: monomer ; 582.3640 [M]+
C₃₂H₄₈N₅O₅
Location inside paper: Fig. 5, C
Compound class: nucleoside
Contained glycoepitopes: IEDB_149136
 
Methods: MS/MS, LC-MS, ESI-QTOF-MS, cell growth, sonication, centrifugation, ion chromatography, UHPLC, PCA, PLS-DA
 
Related record ID(s): 49306, 49307, 49309
NCBI Taxonomy refs (TaxIDs): 83332, 1773
Show glycosyltransferases
 

Convert structure to SMILES & 3D GlycoCT β-test WURCS 2.0 GLYCAM GlycoCT (external) GlycoCT XML (ext) GlydeII XML LinUCS Fragmentize Mol. weight

Simulate NMR spectra (GODDESS)

Show Sweet-II 3D model Generate 3D coords by GLYCAM

Taxonomic group: bacteria / Actinobacteria (Phylum: Actinobacteria)
Associated disease: infection due to Mycobacterium tuberculosis [ICD11: XN1N2 ]
 
NCBI PubMed ID: 26038762
Publication DOI: 10.1038/emi.2015.6
Journal NLM ID: 101594885
Publisher: Philadelphia, PA: Taylor & Francis
Correspondence: Lau SK <skplauhkucc.hku.hk>; Woo PC <pcywoohkucc.hku.hk>
Institutions: State Key Laboratory of Emerging Infectious Diseases, Hong Kong, China, Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China, Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China, Department of Microbiology, The University of Hong Kong, Hong Kong, China, Department of Pathology, The University of Hong Kong, Hong Kong, China

Although previous studies have reported the use of metabolomics for Mycobacterium species differentiation, little is known about the potential of extracellular metabolites of Mycobacterium tuberculosis (MTB) as specific biomarkers. Using an optimized ultrahigh performance liquid chromatography-electrospray ionization-quadruple time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) platform, we characterized the extracellular metabolomes of culture supernatant of nine MTB strains and nine non-tuberculous Mycobacterium (NTM) strains (four M. avium complex, one M. bovis Bacillus Calmette-Guérin (BCG), one M. chelonae, one M. fortuitum and two M. kansasii). Principal component analysis readily distinguished the metabolomes between MTB and NTM. Using multivariate and univariate analysis, 24 metabolites with significantly higher levels in MTB were identified. While seven metabolites were identified by tandem mass spectrometry (MS/MS), the other 17 metabolites were unidentified by MS/MS against database matching, suggesting that they may be potentially novel compounds. One metabolite was identified as dexpanthenol, the alcohol analog of pantothenic acid (vitamin B5), which was not known to be produced by bacteria previously. Four metabolites were identified as 1-tuberculosinyladenosine (1-TbAd), a product of the virulence-associated enzyme Rv3378c, and three previously undescribed derivatives of 1-TbAd. Two derivatives differ from 1-TbAd by the ribose group of the nucleoside while the other likely differs by the base. The remaining two metabolites were identified as a tetrapeptide, Val-His-Glu-His, and a monoacylglycerophosphoglycerol, phosphatidylglycerol (PG) (16:0/0:0), respectively. Further studies on the chemical structure and biosynthetic pathway of these MTB-specific metabolites would help understand their biological functions. Studies on clinical samples from tuberculosis patients are required to explore for their potential role as diagnostic biomarkers

specific, Mycobacterium tuberculosis, metabolomics, diagnosis, biomarkers

Structure type: monomer ; 530.3730 [M]+
C₂₉H₄₈N₅O₄
Location inside paper: Fig. 5, D
Compound class: nucleoside
Contained glycoepitopes: IEDB_149136
 
Methods: MS/MS, LC-MS, ESI-QTOF-MS, cell growth, sonication, centrifugation, ion chromatography, UHPLC, PCA, PLS-DA
 
Related record ID(s): 49306, 49307, 49308
NCBI Taxonomy refs (TaxIDs): 83332, 1773
Show glycosyltransferases
 

Convert structure to SMILES & 3D GlycoCT β-test WURCS 2.0 GLYCAM GlycoCT (external) GlycoCT XML (ext) GlydeII XML LinUCS Fragmentize Mol. weight

Simulate NMR spectra (GODDESS)

Show Sweet-II 3D model Generate 3D coords by GLYCAM