Identification of specific metabolites in culture supernatant of Mycobacterium tuberculosis using metabolomics: Exploration of potential biomarkers

Susanna K.P. Lau, Ching Wan Lam, Shirly O.T. Curreem, Kim Chung Lee, Candy C.Y. Lau, Wang Ngai Chow, Antonio H.Y. Ngan, Kelvin K.W. To, Jasper F.W. Chan, Ivan F.N. Hung, Wing Cheong Yam, Kwok Yung Yuen, Patrick C.Y. Woo

Research output: Journal article publicationJournal articleAcademic researchpeer-review

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere6
JournalEmerging Microbes and Infections
Volume4
Issue number1
Early online date28 Jan 2015
DOIs
Publication statusPublished - Jan 2015
Externally publishedYes

Keywords

  • biomarkers
  • diagnosis
  • metabolomics
  • Mycobacterium tuberculosis
  • specific

ASJC Scopus subject areas

  • Parasitology
  • Epidemiology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Virology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Identification of specific metabolites in culture supernatant of Mycobacterium tuberculosis using metabolomics: Exploration of potential biomarkers'. Together they form a unique fingerprint.

Cite this